臺灣博碩士論文加值系統

本研究係探討具有抗發炎能力與調節 T helper (Th)1 和 Th2 免疫反應，以及雌激素受器調節劑 (selective estrogen receptor modulator, SERM) 的植物食材樣品，對於自體免疫傾向鼠病情的影響。首先以 BALB/c 正常小鼠的初代腹腔細胞，篩選具有降低 lipopolysaccharide (LPS) 刺激下 interleukin(IL)-1β、IL-6 與 tumor necrosis factor (TNF)-α 等促發炎細胞激素分泌量之抗發炎潛力樣品，再以 LPS 誘發的急性發炎模式，檢測這些樣品 in vivo 是否降低促發炎細胞激素的分泌量，因而改善發炎反應。篩選結果顯示，經發酵三天的黑豆乙酸乙酯萃取物 (fermented black soybean methanol extracts, F3BME) 與苜蓿芽乙酸乙酯萃物 (alfalfa sprouts ethyl acetate extracts, ASEA) 明顯抑制促發炎細胞激素的分泌量，並且增加 LPS 致急性發炎小鼠的存活率。由於 18 週齡相較 9 週齡的 MRL-lpr/lpr 小鼠之脾臟細胞，在 Con A 刺激下 interferon (IFN)-γ 與 IL-10 的分泌量明顯增加，表示這些細胞激素與病程的發展有關，接續以 16~18 週齡 MRL-lpr/lpr 小鼠的初代細胞，檢測篩選樣品對於細胞激素的影響，樣品包括 F3BME、ASEA、以及山藥乙酸乙酯萃物 (Dioscorea alata L. ethyl acetate extracts, DAEA)。結果表示 50 mg/ml ASEA 或 40 mg/ml DEAE 顯著降低脾臟細胞在 Con A 刺激下 IFN-γ、IL-4 與 IL-10 的分泌量，40 mg/ml F3BME 則只有降低 IFN-γ 的分泌量。同時， ASEA 與 F3BME 可以抑制腹腔細胞在 LPS 刺激下促發炎細胞激素的分泌量， DEAE 則只降低 IL-6 的分泌量。在 CHO-K1 細胞的 estrogen receptor (ER) 轉錄活性分析中， 50 mg/ml ASEA 活化 ERβ 的能力高於活化 ERα 的能力，表示有 SERM 的能力；同時， ASEA 可以抑制雌激素促進 MCF-7 細胞增生的作用，具有拮抗雌激素之作用。綜合以上結果， ASEA 可能有助於自體免疫病情的改善，因此以 ASEA 介入 MRL-lpr/lpr 小鼠的飲食中，測試能否緩和小鼠的病程發展。實驗一將 12 週齡 MRL-lpr/lpr 小鼠依據體重、尿蛋白與血清抗雙股 DNA IgG 抗體分成五組。分別為控制組 (Control) 與苜宿芽粉組 (AS)、苜蓿芽乙酸乙酯萃物組 (ASEA, 25 mg/kg BW)、香豆素 coumestrol 組 (CUM, 0.075 mg/kg BW)、與 tamoxifen 組 (TAM, 0.375 mg/kg BW)， 各組管餵葵花油 (Control 與 AS 組) 或含有待測樣品的葵花油，每天管餵量為 50 ml ，每週共管餵 6 天，各組餵食的飼料皆為 AIN-76 配方，AS 組的飼料額外添加 5.5% 的苜蓿芽粉。結果顯示，ASEA 組與 TAM 組可以降低血清 anti-dsDNA IgG2a/IgG1 比率，抑制血清 IL-12p40 的含量，降低尿蛋白的發生率，而且提高小鼠的存活率。AS 組與 CUM 組並未影響 MRL-lpr/lpr 小鼠的病情發展。因此實驗二再次將 12 週齡 MRL-lpr/lpr 小鼠分成三組，分別是 Control組、 ASEA 組與 TAM 組，飼料、管餵劑量與時程與上述實驗相同。在管餵補充六週後，犧牲小鼠進行分析，結果顯示，ASEA 組與 TAM 組顯著降低血清 IL-12p40 與 IL-6 的生成，同時延後尿蛋白的發生，與實驗一結果一致。在免疫細胞分析方面，ASEA 組相較於 Control 組，脾臟細胞在 Con A 刺激下 IFN-γ、IL-4 與 IL-6 的分泌量顯著降低，腹腔細胞在 LPS 刺激下促發炎細胞激素的分泌量有略低的趨勢，而且脾臟細胞中的 CD3+CD69+ T 細胞族群明顯減少。腎臟切片圖顯示 ASEA 組的間質細胞的增生與絲球體腫大程度較 Control 組輕微。為了解 ASEA 中的生物活性分子，遂進行分離與純化，將 ASEA 以開放式矽膠管柱層析與製備式 HPLC 的分離，經過抗發炎與 SERM 活性鑑定，取得具抗發炎能力的 loliolide 2.5 mg 與 4-hydroxy-6-nonadecyl-2H-pyran-2-one 1.9 mg，以及具抗發炎和 SERM 活性的 liquiritigenin 2.1 mg 與isoliquiritigenin 5.2 mg。本研究中檢測抗發炎能力與 SERM 能力、以及抑制自體免疫傾向小鼠細胞分泌 IFN-γ 和 Th2 細胞激素的能力，篩選出苜蓿芽乙酸乙酯萃物 ASEA，在 in vivo 中明顯改善 MRL-lpr/lpr 鼠體內的發炎狀況，而有助於延緩病情的發展。自分離純化 ASEA 結果可知，loliolide、4-hydroxy-6-nonadecyl-2H-pyran-2-one、liquiritigenin、與 isoliquiritigenin 可能為延緩病情的主要化合物。

關鍵字: 自體免疫、發炎、MRL-lpr/lpr、苜蓿芽乙酸乙酯萃取物、促發炎細胞激素、雌激素受器調節劑

The purpose of this study was to investigate the effect of plant food components sample possessing the abilities of anti-inflammation, Th1/Th2 immune regulation, and selective estrogen receptor modulator (SERM) on the autoimmune-prone disease in MRL-lpr/lpr female mice. First, in primary cell culture test, potential plant food components which could inhibit LPS-stimulated pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α, secretion from peritoneal macrophages of BALB/c mice were screened out. These potential food components were subsequently tested (per oral) to reduce serum levels of pro-inflammatory cytokines and attenuate inflammatory conditions in a murine model of LPS-induced acute inflammation. The results showed fermented 3-day blacksoybean methanol extract (F3BME) and alfalfa sprouts ethyl acetate extract (ASEA) could inhibit pro-inflammatioy cytokines secretion in vitro and in vivo.

Due to significantly higher IFN-γ and IL-10 secretion from Con A-stimulated splenocytes at age 18 weeks compared to those at age of 9 weeks in MRL-lpr/lpr mice, we cultured primary cells of MRL-lpr/lpr mice at age of 16~18 weeks and tested anti-inflammatory and Th1/Th2 immune-regulatiory abilities of potential food components. The results showed 50 mg/ml ASEA and 40 mg/ml DAEA could significantly reduce IFN-γ, IL-4, and IL-10 secretions from Con A-stimulated splenocytes of MRL-lpr/lpr mice, and 40 mg/ml F3BME just inhibited IFN-γ secretion from these cells. ASEA and F3BME could evidently inhibit LPS-stimulated pro-inflammatory cytokine secretions peritoneal exudates cells (PEC) of MRL-lpr/lpr mice, and DAEA only inhibited IL-6 secretion from these cells. Moreover, estrogen receptor (ER)β rather than ERα is activated by 50 mg/ml ASEA in CHO-K1 ER transactivation assay. This revealed ASEA likely be a SERM. ASEA also inhibited MCF-7 cell proliferation under 1 nM 17β-estradiol treatment. These data displayed ASEA have the potential to ameliorate inflammatory status and estrogen-related disease course in MRL-lpr/lpr mice.

twelve-week-old MRL-lpr/lpr mice depend on their body weight, urine protein levels and sera levels of anti-dsDNA IgG were divided into five groups, Control group (50 ml sunflower oil (SO)/day), AS group (50 ml SO/day), ASEA group (25 mg/kg BW), CUM group (coumestrol, 0.075 mg/kg BW), TAM group (tamoxifen citrate, 0.375 mg/kg BW). The mice in each group were tube-fed either SO or tested samples in SO (50 ml/day) six days per week. Each group was fed AIN-76 diet, but the AS group was fed AIN-76 diet plus containing 5.5% alfalfa sprouts dry powder. The results exhibited that ratio of sera IgG2a/IgG1, sera levels of IL-12p40 and appearance of proteinuria were reduced, and life span was extended in the ASEA and the TAM groups. The disease progress of mice was not affected in the AS and the CUM groups. Subsequently, to clarify ASEA how to improve the disease development of MRL-lpr/lpr mice, we sacrifice mice after supplementation of tested sample for six weeks. The results illustrated sera levels of IL-12p40 and IL-6 and appearance of proteinuria were reduced in the ASEA and the TAM groups. Con A-stimulated IFN-γ, IL-4 and IL-6 secretion from splenocytes were evidently attenuated in the ASEA group compared to the control. These data are in accordance with in vitro results. CD3+CD69+ T cell population of splenocytes was remarkable decreased in the ASEA group. The ASEA group also had less severe glomerulonephritis.

To clarify what bioactive compounds in ASEA, this study purified ASEA (71 g) by silica gel chromatography and prepared HPLC separation. By using anti-inflammatory test and CHO-K1 ER transactivation assay, the candidate compounds were verified and identified as loliolide, 4-hydroxy-6-nonadecyl-2H-pyran-2-one, liquiritigenin, and isoliquiritigenin.

In summary, this study demonstrated that ASEA having the abilities of anti-inflammation, Th1 and Th2 immune regulation and SERM could strikingly reduce the inflammatory progress and ameliorate disease course in autoimmune-prone MRL-lpr/lpr mice. Some purified compounds in ASEA such as loliolide, 4-hydroxy-6-nonadecyl-2H-pyran-2-one, liquiritigenin, and isoliquiritigenin are supposed to the contribution of disease amelioration.



Key words: autoimmune, inflammation, MRL-lpr/lpr, ASEA, pro-inflammatory cytokine, SERM

總 目 錄
第 一 章 文 獻 回 顧 1
第一節 發炎反應 1
一. 簡介 1
二. 發炎的過程 2
三. T 細胞的活化 4
四. 調節發炎反應之細胞激素 6
第二節 自體免疫反應與全身性紅斑狼瘡 7
一. 免疫系統自體辨識 7
二. 自體免疫疾病的分類 8
三. 全身性紅斑狼瘡疾病特徵與臨床治療 8
四. 全身性紅斑狼瘡的致病因素 11
五. 試驗全身性紅斑狼瘡的動物模式 14
1. NZB/W F1 品系 14
2. BXSB 品系 15
3. MRL-lpr/lpr 品系 15
4. 抗體誘發模式 16
第三節 細胞激素與全身性紅斑狼瘡 19
一. T 與 B 細胞在自體免疫中的反應 19
二. 促進病程發展的細胞激素 22
三. 緩和病程發展的細胞激素 24
第四節 雌激素、雌激素受器與全身性紅斑狼瘡 26
一. 雌激素受器分子 (estrogen receptor) 26
1. ERα 的介紹 26
2. ERβ 的介紹 27
3. ERα 與 ERβ在組織中的分佈 27
二. 選擇性雌激素受器調節劑 (selective estrogen receptor modulator, SERM) 29
三. 雌激素受器分子與 SLE 模式小鼠的文獻回顧 31
四. 選擇性雌激素作用劑在發炎性疾病與自體免疫疾病上的應用 32
第五節 飲食因子對於自體免疫疾病與發炎反應的影響 33
一. 飲食因子 33
二. 富含植物雌激素的食材 35
第六節 研究動機與架構 36
第 二 章 以急性發炎小鼠模式中細胞激素的變化作為評估抗發炎的指標 38
第一節 前 言 38
第二節 材料與方法 39
一. 實驗設計 39
二. 實驗材料 40
1. 生化試劑 40
2. 小鼠巨噬細胞株 RAW 264.7 與實驗動物 40
三. 實驗方法 40
1. 巨噬細胞株 RAW 264.7 的培養 40
2. MTT染色法測定細胞存活率 41
3. LPS 致急性發炎動物模式 41
4. 血液樣本的採集 42
5. 腹腔細胞之取得與培養 42
6. 脾臟細胞之取得及培養 43
7. 細胞激素量的測定 44
四. 統計方法 45
第三節 結 果 46
一. 腹腔注射LPS的BALB/c小鼠血清中TNF-α、IL-6與IL-1β的生成 46
二. PDTC降低小鼠血清促發炎細胞激素量 46
三. PDTC 影響急性發炎小鼠初代細胞的細胞激素生成量 47
四. PDTC 增加急性發炎小鼠的存活率 48
五. LPS 致急性發炎的小鼠存活時間與血清細胞激素量的相關性 48
第四節 討 論 56
一. BALB/c 小鼠以 15 mg/kg BW LPS致急性發炎的細胞激素與存活率資料 56
二. 促發炎細胞激素與存活率的相關性 56
三. 研究飲食因子改善急性發炎模式下 LPS 的適用劑量 57
四. 抗發炎試劑PDTC調節細胞激素的生成以及提高存活率 57
第 三 章 具調節細胞激素分泌的食材萃取物對急性發炎模式的影響 58
第一節 前 言 58
第二節 材料與方法 59
一. 實驗設計 59
二. 實驗材料 60
1. 實驗動物 60
2. 發酵的黑豆萃取物 60
3. 苜蓿芽萃取物 61
4. 山藥萃取物 61
5. 生化試劑 62
三. 實驗方法 62
四. 統計方法 64
第三節 結 果 64
一. 植物食材對裂殖素刺激的 BALB/c 小鼠初代細胞分泌細胞激素的影響 64
二. 篩選樣品對 LPS 誘發急性發炎小鼠的影響 67
第四節 討 論 80
一. 植物食材萃取物與異黃酮 (isoflavones) 對細胞激素的影響 80
二. 細胞與組織總細胞的比例推算動物劑量之可行性 81
第 四 章 以自體免疫小鼠初代細胞分泌細胞激素的活性篩選植物食材 82
第一節 前 言 82
第二節 材料與方法 83
一. 實驗材料 83
二. 實驗方法 84
三. 統計方法 88
第三節 結 果 88
一. MRL-lpr/lpr小鼠在不同週齡初代細胞的細胞激素分泌量 88
二. 植物食材對 MRL-lpr/lpr 小鼠初代細胞的細胞激素分泌量之影響 89
三. 苜蓿芽乙酸乙酯萃取物可以抑制雌激素促細胞增生的作用 91
第四節 討 論
一. 自體免疫小鼠 MRL-lpr/lpr 與正常小鼠 BALB/c 99
二. 細胞與組織總細胞的比例推算給予動物的劑量之可行性 99
三. 植物食材對於雌激素受器 subtype 選擇性活化的情形 (SERM) 100
四. 選擇 ASEA 介入 MRL-lpr/lpr 動物實驗 101
第 五 章 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 自體免疫鼠病情的影響 103
第一節 前 言 103
第二節 材料與方法 104
一. 實驗設計 104
二. 自體免疫小鼠品系與飼養 105
三. 病情指標之測定 107
四. 統計方法 116
第三節 結 果 116
一. 試驗樣品對於 MRL-lpr/lpr 品系病程發展之影響 116
二. 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 品系病程發展的調節反應 128
三. 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 品系體內免疫細胞反應 129
四. 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 品系體內雌激素代謝物的影響 131
五. 試驗樣品對於 NZB/W F1 品系的影響 132
第四節 討 論 150
一. 探討苜蓿芽乙酸乙酯萃取物如何緩和 MRL-lpr/lpr 品系小鼠的病情發展 150
二. MRL-lpr/lpr小鼠病情指標與生命期的相關性 151
三. Coumestrol 的補充降低尿蛋白發生卻未影響病程的發展 152
四. 苜蓿芽粉對 MRL-lpr/lpr 小鼠病情的影響 153
第 六 章 苜蓿芽乙酸乙酯萃取物中抗發炎成分的分離與純化 155
第一節 前 言 155
第二節 材料與方法 156
一. 實驗設計 156
二. 實驗材料 157
三. 實驗方法 158
四. 統計方法 159
第三節 結 果 160
一. 苜蓿芽一般成份分析 160
二. 苜蓿芽乙酸乙酯萃取物區分純化、結構鑑定 160
第四節 討 論 176
一. 大量萃取物的分離與純化 176
二. 純化的化合物之炕發炎能力 176
第 七 章 綜合討論與總結 179
第一節 綜合討論 179
一. 苜蓿芽的飲食 179
二. 苜蓿芽乙酸乙酯萃物的抗發炎活性 180
三. 苜蓿芽乙酸乙酯萃物的選擇性雌激素活性 181
第二節 總結 181
附 錄 182
參考文獻 187

















圖 目 錄
圖 1-1 第一型與第二型 T 輔助細胞激素和巨噬細胞活化的關係 5
圖 1-2 狼瘡病理機制的模式 21
圖 1-3 人類 ERα 與 ERβ 構造功能區域 28
圖 1-4 ERα 與 ERβ 的功能區域的相似性 29
圖 1-5 研究架構 37
圖 2-1 第二章實驗流程 39
圖 2-2 BALB/c小鼠在腹腔注射 LPS 後血清促發炎細胞激素生成時程圖 49
圖 2-3 巨噬細胞株 RAW264.7 在 LPS 刺激下促發炎細胞激素的生成時程圖 (A)與在PDTC添加下對促發炎細胞激素的影響 (B) 50
圖 2-4 PDTC對於 LPS 致急性發炎小鼠血清促發炎細胞激素含量的影響 51
圖 2-5 LPS致急性發炎小鼠腹腔細胞的促發炎細胞激素生成量 52
圖 2-6 LPS致急性發炎小鼠脾臟細胞的Th1與Th2細胞激素生成量 53
圖 2-7 PDTC對於 LPS 致急性發炎小鼠的存活影響 54
圖 2-8 急性發炎小鼠存活時間與血清細胞激素生成量的相關性 55
圖 3-1 第三章實驗流程 59
圖 3-2 試驗樣品處理 BALB/c 小鼠腹腔細胞對細胞存活的影響 69
圖 3-3 黑豆萃取物對 BALB/c 小鼠腹腔細胞分泌細胞激素的影響 70
圖 3-4 苜蓿芽萃取物對 BALB/c 小鼠腹腔細胞分泌細胞激素的影響 71
圖 3-5 黑豆萃取物對 BALB/c 小鼠脾臟細胞分泌細胞激素的影響 72
圖 3-6 苜蓿芽萃取物對 BALB/c 小鼠脾臟細胞分泌細胞激素的影響 73
圖 3-7 Genistin、genistein 或coumestrol 對腹腔細胞分泌促發炎細胞激素的影響 74
圖 3-8 補充發酵黑豆萃物對 LPS 致急性發炎小鼠血清促發炎細胞激素含量影響 76
圖 3-9 補充發酵黑豆萃取物可以提高 LPS 致急性發炎小鼠的存活率 77
圖 3-10 補充 ASEA 對 LPS 致急性發炎小鼠血清促發炎細胞激素含量的影響 78
圖 3-11 補充 ASEA 可以提高 LPS 致急性發炎小鼠的存活率 79
圖 4-1 MRL-lpr/lpr 小鼠在不同週齡時血清與脾臟細胞的細胞激素生成量 92
圖 4-2 測試樣品對 18 週齡MRL-lpr/lpr鼠脾臟細胞分泌 IFN-γ 與 IL-10 的影響 94
圖 4-3 測試樣品對 18 週齡MRL-lpr/lpr 鼠脾臟細胞分泌 IL-2 與 IL-4 的影響 95
圖 4-4 測試樣品對 18 週齡MRL-lpr/lpr 鼠腹腔細胞分泌促發炎細胞激素的影響 96
圖 4-5 雌激素促進 18週齡 MRL-lpr/lpr 小鼠初代細胞分泌 IL-10 或 TNF-α 透過 estrogen receptor 97
圖 4-6 苜蓿芽乙酸乙酯萃物對雌激素促進 MCF-7 與 Ishikawa 細胞增生的影響 98
圖 5-1 補充各樣品對 MRL-lpr/lpr 小鼠的體重與每日平均攝食量的影響 120
圖 5-2 試驗樣品對 MRL-lpr/lpr 雌鼠血清抗dsDNA IgG 及IgM 含量的影響 121
圖 5-3 試驗樣品對 MRL-lpr/lpr 雌鼠血清 anti-dsDNA IgG2a、IgG1與兩者相對比率的影響 122
圖 5-4 試驗樣品對 MRL-lpr/lpr 雌鼠血清抗心磷脂 IgG 含量的影響 123
圖 5-5 試驗樣品對 MRL-lpr/lpr 雌鼠血清 IL-12p40 含量的影響 124
圖 5-6 試驗樣品對MRL-lpr/lpr雌鼠的蛋白尿發生率與尿液白蛋白含量的影響 126
圖 5-7 試驗樣品對 MRL-lpr/lpr 雌鼠各週齡存活率與整體生命期的影響 127
圖 5-8 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠的蛋白尿發生率與尿液白蛋白含量的影響 139
圖 5-9 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠腎臟絲球體腎炎的影響 140
圖 5-10 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠尿液雌激素代謝物的影響 146
圖 5-11 補充各樣品對 NZBW F1 小鼠的體重與每日平均攝食量的影響 147
圖 5-12 試驗樣品對 NZBW F1 雌鼠血清抗dsDNA IgG 及抗cardiolipin IgG 含量的影響 148
圖 5-13 補充試驗樣品對 NZB/W F1 雌鼠的尿蛋白發生 (A) 與小鼠存活率 (B) 149
圖 6-1 第六章實驗流程 156
圖 6-2 苜蓿芽乙酸乙酯萃物對 RAW264.7 巨噬細胞分泌 IL-6 的影響 165
圖 6-3 苜蓿芽乙酸乙酯萃物區分物對 RAW264.7 巨噬細胞分泌 IL-6 的影響 166
圖 6-4 苜蓿芽乙酸乙酯萃物 F23~F28 對 RAW264.7 巨噬細胞分泌 IL-6 的影響 167
圖 6-5 苜蓿芽乙酸乙酯萃物單離區分物 F23-14-2-2 1H-NMR 與 13C-NMR 圖譜 168
圖 6-6 苜蓿芽乙酸乙酯萃物單離區分物 F23-14-3-3 1H-NMR 與 13C-NMR 圖譜 169
圖 6-7 苜蓿芽乙酸乙酯萃物 F28~F31 對 RAW264.7 巨噬細胞分泌 IL-6 的影響 170
圖 6-8 苜蓿芽乙酸乙酯萃物F28-20-1~F28-20-4 對 RAW264.7 巨噬細胞分泌 IL-6 的影響 171
圖 6-9 苜蓿芽乙酸乙酯萃物單離區分物 F28-20-1-3 1H-NMR 與 13C-NMR 圖譜 172
圖 6-10 六種化合物對 BALB/c 脾臟細胞分泌 IFN-γ與 IL-4 的影響 173
圖 6-11 六種化合物對 BALB/c 腹腔細胞分泌 IL-6 與 IL-1β 的影響 174
圖 6-11 苜蓿芽乙酸乙酯萃物的分離與純化 175



























表 目 錄
表 1-1 根據 1982 年美國風濕學院制定的全身性紅斑狼瘡之診斷要項 10
表 1-2 與 SLE 疾病相關的基因 12
表 1-3 NZB/W F1 小鼠的疾病特徵 17
表 1-4 MRL-lpr/lpr 小鼠的疾病特徵 18
表 1-5 雌激素受器配體在各組織的生物活性 30
表 1-6 ERβ 作用劑的藥物潛力 33
表 3-1 細胞組織比例換算小鼠的餵食劑量 64
表 3-2 各植物食材影響 BALB/c 小鼠初代細胞分泌細胞激素的總整理 75
表 4-1 MRL-lpr/lpr小鼠在9週齡與18週齡時腹腔細胞在LPS刺激下的細胞激素分泌量 93
表 4-2 各植物食材影響 MRL-lpr/lpr 小鼠初代細胞分泌細胞激素的總整理 102
表 5-1 實驗飼料組成表 106
表 5-2 試驗樣品對 MRL-lpr/lpr 雌鼠血清三酸甘油酯與膽固醇含量的影響 125
表 5-3 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠體重、體重增加量、攝食量與飼料利用率的影響 134
表 5-4 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠組織重量與相對組織重量的影響 135
表 5-5 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠組織的 TBARS 數值影響 136
表 5-6 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠血清中自體抗體含量的影響 137
表 5-7 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠血清中細胞激素含量的影響 138
表 5-8 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠腹腔、脾臟以及皮耶氏淋巴結細胞數目的影響 141
表 5-9 苜蓿芽乙酸乙酯萃物對MRL-lpr/lpr雌鼠腹腔細胞促發炎細胞激素的影響 142
表 5-10 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠脾臟細胞生成細胞激素的影響 143
表 5-11 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠脾臟細胞增生的影響 144
表 5-12 苜蓿芽乙酸乙酯萃物對 MRL-lpr/lpr 雌鼠脾臟細胞表面標記表現的影響 145
表 6-1 苜蓿芽一般成份分析 160
表 6-2 苜蓿芽乙酸乙酯萃取物經矽膠管柱以不同極性沖堤液流洗之區分物收取量 164

王姿晴 促進或抑制巨噬細胞株分泌前列腺素 E2 的食材對發炎反應的影響, 國立台灣大學微生物與生化學研究所 碩士論文 (2007)
吳俊億 利用根黴菌開發機能性醱酵黑豆食品之研究, 國立台灣大學微生物與生化學研究所 碩士論文 (2003)
洪永瀚、林璧鳳: 稻苗草榨汁對於抑制發炎反應的功能研究, 台灣農業化學與食品科學 2004; 42(6): 456-465.
鄭瑋宜 山藥具雌激素活性之單離與鑑定研究, 國立台灣大學微生物與生化學研究所 博士論文 (2007)
羅文音 以卵蛋白致敏小鼠模式探討攝食山藥對過敏性氣喘的影響, 國立台灣大學微生物與生化學研究所 碩士論文 (2006)
Akahoshi M, Nakashima H, Tanaka Y, et al. Th1/ Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum 1999; 42:1644-1648.
Akaogi J, Barker T, Kuroda Y, et al. Role of non-protein amino acid L-canavanine in autoimmunity. Autoimmun Rev 2006; 5: 429-435.
Alcocer-Varela J, Iglesias A, Llorente L, Alarcon-Segovia D. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum 1985; 28: 52-57.
Al-Janadi M, Al-Balla S, Al-Dalaan A, Raziuddin S. Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases. J Clin Immunol 1993; 13: 58-67.
Alleva DJ, Kaser SB, Beller DI. Aberrant cytokine expression and autocrine regulation characterize macrophages from young MRL+/+ and NZB/W F1 lupus-prone mice. J Immunol 1997; 159: 5610-5619.
Apelgren LD, Bailey DL, Fouts RL, et al. The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL-lpr/lpr mice. Cell Immunol 1996; 173: 55-63.
Aringer M, Smolen JS. Cytoikne expression in lupus kidneys. Lupus 2005; 14: 13-18.
Aringer M, Zimmermann C, Graninger WB, Petera P, Steiner G, Smolen JS. Anti-TNF therapy of SLE is feasible and apparently effective. Arthritis Rheum 2003; 48: S378 (abstract).
Asanuma Y, Chung CP, Oeser A, et al. Increased concentration of proatherogenic inflammatory cytokines in systemic lupus erythematosus: relationship to cardiovascular risk factors. J Rheumatol 2006; 33: 539-545.
Auborn KJ, Qi M, Yan XJ, et al. Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplementated with indole-3-carbinol. J Nutr 2003; 133: 3610-3613.
Balomenos D, Rumold R, Theofilopoulos AN. Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. J Clin Invest 1998; 101: 364-371.
Bardana EJ Jr, Malinow MR, Houghton DC, et al. Diet-induced systemic lupus erythematosus (SLE) in primates. Am J Kidney Dis 1982; 1: 345-352.
Baumann H, Gauldie J. The acute phase response. Immunology Today 1994; 15: 74-80.
Beebe AM, Cua DJ, Marlefyt RW. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine and Growth Factor Rev 2002; 13: 403-412.
Blank M, Krup M, Mendlovic S, et al. The importance of the pathogenic 16/6 idiotype in the induction of SLE in naive mice. Scand J Immunol 1990; 31: 45-52.
Blanque’ R, Millet S, Gardner CR. Hypothermia as an indicator of the acute effects of lipopolysaccharides: Comparison with serum levels of IL-1, IL-6 and TNF-α. Gen Pharmac 1996; 27: 973-977.
Blanque’ R, Meakin C, Millet S, Gardner CR. Dual mechanisms of action of interferon-γ potentiating responses to LPS in mice IL-1, TNF-α and IL-6 production in serum and hypothermia. Gen Pharmac 1999; 32: 453-461.
Boue SM, Wiese TE, Nehls S, et al. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem 2003; 51: 2193-2199.
Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-Hydroxyestrone: the good estrogen. J Endocrinol 1996; 150: 5259-5265.
Brennan DC, Yui MA, Wuthrich RP, Kelley VE. Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. J Immunol 1989; 143: 3470-3475.
Burke TR. Protein-tyrosine kinase inhibitors. Drugs Future 1992; 17: 119-131.
Buras JA, Holzman B, Sitkovsky M. Animal models of sepsis: setting the stage. Nat Rev Drug Discov 2005; 4: 854-865.
Burger D, Dayer JM. Cytokines, acute-phase proteins, and hormones. IL-1 and TNF-alpha production in contact-mediated activation of monocytes by T lymphocytes. Ann N Y Acad Sci 2002; 966: 464-473.
Bynoe M, Grimaldi C, Diamond B. Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells. Proc Natl Acad Sci USA 2000; 97: 2703-2708.
Bynoté KK, Hackenberg JM, Korach KS, Lubahn DB, Lane PH, Gould KA. Estrogen receptor-alpha deficiency attenuates autoimmune disease in (NZB x NZW)F1 mice. Genes Immun 2008; 9:137-152.
Casciola-Rosen L, Andrade F, Ulanet D, Wong WB, Rosen A. Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity. J Exp Med 1999; 190: 815-826.
Carlsten H, Tarkowski A, Holmdahl R, Nilsson LA. Oestrogen is a potent disease accelerator in SLE-prone MRL-lpr/lpr mice. Clin Exp Immunol 1990; 80: 467-473.
Castagnetta LA, Carruba G, Granata OM. Increased estrogen formation and estrogen to androgen ratio in the synovial fluid of patients with rheumatoid arthritis. J Rheumatol 2003; 30: 2597-2605.
Chan MY, Ho CT, Huang HI. Effects of three dietary phytochemicals from tea, rosemary and turmeric on inflammation-induced nitrite production. Cancer Lett 1995; 96: 23-29.
Chan O, Shlomchik MJ. A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol 1998; 160: 50-59.
Chen YY, Suen JL, Wu WM, Chiang BL. The effect of cytokines on the activation-induced apoptosis of B cells in autoimmune NZB/W F1 mice. Scand J Immunol 2001; 53: 596-601.
Cheng WY, Kuo YH, Huang CJ. Isolation and identification of novel estrogenic compounds in yam tuber (Dioscorea alata Cv. Tainung No. 2). J Agric Food Chem 2007; 55: 7350-7358.
Cohen DL, Eisenbery RA. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferation diseases. Annu Rev Immunol 1991; 9: 243-269.
Cole H, Halnan KE. Facilitation of tumour spread in irradiated tissue after prophylactic post-operative x-ray therapy for breast cancer. Clin Radiol 1971; 22: 133-135.
Cosentino G, Soprana E, Thienes CP, Siccardi AG, Viale G, Vercelli D. IL-13 down-regulates CD14 expression and TNF-α secretion in normal human monocytes. J Immunol 1995; 155: 3145-3151.
Couse JF, Korach KS. Estrogen receptor-alpha mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract. Toxicology 2004; 205: 55-63.
Cremer L, Herold A, Avram D, Szegli G. A purified green barley extract with modulatory properties upon TNF-α and ROS released by human specialized cells isolated from RA patients. Roum Arch Microbiol Immunol 1998; 57: 231-242.
Cristofaro PA, Opal SM, Palardy JE, et al. WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock. Crit Care Med 2006; 34: 2188-2193.
Csiszar AG, Nagy P, Gergely T, Pozsonyi, Pocsik E. Increased interferon-gamma (IFN-gamma), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 2000; 122: 464-470.
Cutis SH, Korach KS. Steroid receptor knockout models: phenotypes and responses illustrate interactions between receptor signaling pathways in vivo. Adv Pharmacol 2000; 47: 357-380.
Cutolo M, Villaggio B, Montagna P. Synovial fluid estrogens in rheumatoid arthritis. Autoimmun Rev 2004; 3: 193-198.
Cuzzocrea S, Chaterjee PK, Mazzon E, et al. Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation. Br J Pharmacol 2002; 135: 496-510.
Davas EM, Tsirogianni A, Kappou I, Karamitsos D, Economidou I, Dantis PC. Serum IL-6, TNFalpha, p55 srTNFalpha, p75 srTNFalpha, srIL-2alpha levels and disease activity in systemic lupus erythematosus. Clin Rheumatol 1999; 18: 17-22.
Dayan M, Zinger H, Kalush F, et al. The beneficial effects of treatment with tamoxifen and anti-oestradiol antibody on experimental systemic lupus erythematosus are associated with cytokine modulations. Immunology 1997; 90: 101-108.
Dhaher YY, Greenstein B, de Fougerolles Nunn E, Khamashta M, Hughes GR. Strain differences in binding properties of estrogen receptors in immature and adult BALB/c and MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus. Int J Immunopharmacol 2000; 22: 247-254.
Doria A, Ghirardello A, Iaccarino L, et al. Pregnancy, cytokines, and disease activity in systemic lupus erythematosus. Arthritis Rheum 2004; 51: 989-995.
Drake CG, Babcock SK, Palmer E, Kotzin BL. Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB × NZW) F1 mice. Proc Natl Acad Sci USA 1994; 91: 4062-4066.
Drappa J, Brot N, Elkon KB. The Fas protein is expressed at high levels on CD4+ CD8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, MRL-lpr/lpr. Proc Natl Acad Sci USA 1993; 90: 10340-10344.
Duan H, Takaishi Y, Momota H, Takao Taki Y. Immunosuppressive constituents from Saussurea medusa. Phytochemistry 2002; 59: 85-90.
Edwards CK 3rd, Zhou T, Zhang J, et al. Inhibition of superantigen-induced proinflammatory cytokine production and inflamatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha. J Immunol 1996; 157: 1758-1772.
Elloso MM, Phiel K, Henderson RA, Harris HA, Adelman SJ. Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligands. J Endocrinol 2005; 185: 243-252.
Fan JL, Himeno K, Tsuru S, Nomoto K. Treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin. Clin Exp Immunol 1987; 70: 94-101.
Fernandes G, Friend P, Yunis EJ, Good RA. Influence of diet on survival of mice. Proc Natl Acad Sci USA 1978; 75: 1500-1506.
Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371-1388.
Folomeev M, Dougados M, Beaune J. Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. Lupus 1992; 1: 191-195.
Foster S, Duke JA. A Field Guide to Medicinal Plants and Herbs: Eastern and Central North America. In: Peterson RT (ed), Houghton Mifflin Co., 1990, 211.
Forster C, Makela S, Warri A, et al. Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci USA 2002; 99: 15578-15583.
Francucci CM, Romagni P, Boscaro M. Raloxifene: bone and cardiovascular effects. J Endocrinol Invest 2005; 28(10 Suppl): 85-89.
Furuya Y, Kawakita T, Nomoto K. Immunomodulating effect of a traditional Japanese medicine, hachimi-jio-gan (ba-wei-di-huang-wan), on Th1 predominance in autoimmune MRL/MP-lpr/lpr mice. Int Immunopharmacol 2001; 1: 551-559.
Gabay C, Cakir N, Moral F, et al. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol 1997; 24: 303-308.
Galanos C, Luderitz Q, Rietschel ET, et al. Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. Eur J Biochem 1985; 148: 1-5.
Gilpin DA. Calculation of a new Meeh constant and experimental determination of burn size. Burns 1996; 8: 607-611.
Green S, Walter P, Kumar V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 1986; 320: 134-139.
Greenstein BD, Dhaher YY, Bridges Ede F, et al. Effects of an aromatase inhibitor on thymus and kidney and on oestrogen receptors in female MRL/MP-lpr/lpr mice. Lupus 1993; 4: 221-225.
Greenstein BD, Roa R, Dhaher YY, et al. Estrogen and progesterone receptors in murine models of systemic lupus erythematosus. Int Immunopharmacol 2001; 1: 1025-1035.
Grimaldi CM, Michael DJ, Diamond B. Cutting edge: expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen-induced lupus. J Immunol 2001; 167: 1886-1890.
Gustafsson JA. Steroids and the scientist. Mol Endocrinol 2005; 19(6): 1412-1417.
Gutierrez-Ramos JC, Andreu JL, Revilla Y, Vinuela E, Martinez C. Recovery from autoimmunity of MRL-lpr/lpr mice after infection with an interleukin-2/vaccinia recombinant virus. Nature 1990; 346: 271-274.
Haas C, Ryffel B, Le Hir M. IFN-gamma is essential for the development of autoimmune glomerulonephritis in MRL/lpr mice. J Immunol 1997; 158: 5484-5491.
Haas C, Ryffel B, Le Hir M. IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB × NZW) F1 mice. J Immunol 1998; 160: 3713-3718.
Hall JM, Korach KS. Analysis of the molecular mechanisms of human estrogen receptors alpha and beta reveals differential specificity in target promoter regulation by xenoestrogens. J Biol Chem 2002; 277: 44455-44461.
Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm 2007; 2007: article ID 45673, 10 pages.
Harrington WR, Sheng S, Barnett DH, Petz LN. Katzenellenbogen JA, Katzenellenbogen BS. Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression. Mol Cell Endocrinol 2003; 206: 13-22.
Harris HA, Albert LM, Leathurby Y, et al. Evaluation of an estrogen receptor-ß agonist in animal models of human disease. Endocrinology 2003; 144: 4241-4249.
Hiraga Y, Taino K, Kurokawa M, Takagi R, Ohkata K. (-)-Loliolide and Other Germination Inhibitory Active Constituents in Equisetum Arvense. Nat Prod Lett 1997; 10: 181-186.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
Hodges R, Porte A.L. The structure of loliolide, a terpene from Lolium perenne. Tetrahedron 1964; 20: 1463-1467.
Hong YH, Wang TC, Huang CJ, Cheng WY, Lin BF. Soy isoflavones supplementation alleviates disease severity in autoimmune-prone MRL-lpr/lpr mice. Lupus 2008 (in press).
Hong YH, Chao WW, Wang TC, Lin BF. Alfalfa sprout extracts in ethyl acetate inhibit in vitro and in vivo lipopolysaccharide-induced inflammation. Exp Biol Med 2008 (revised).
Horlick L, Federoff S. Letter: Alfalfa and blood-cholesterol. Lancet 1975; 2: 361-362.
Howard M, Muchamuel T, Andrade S, Menon S. Interleukin-10 protects mice from lethal endotoxemia. J Exp Med 1993; 177: 1205-1208.
Hsieh CC, Lin BF. The effects of vitamin E supplementation on autoimmune-prone New Zealand black x New Zealand white F1 mice fed an oxidised oil diet. Br J Nutr 2005a; 93: 655-662.
Hsieh CC, Lin BF. Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/lpr mice. Nutrition 2005b; 21: 940-948.
Herbert V, Kastan TS. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr 1994; 60(4): 639-640.
Hsu YL, Kuo PL, Lin LT Lin CC. Isoliquiritigenin inhibits cell proliferation and induces apoptosis in human hepatoma cells. Planta Med 2005; 71: 130-134.
Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 1994; 179: 305-310.
Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002; 13: 357-368.
Ito T, Seo N, Yagi H, et al. Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice. J Dermatol Sci 2002; 28: 198-210.
Jabs DA, Burek CL, Hu Q, Cuppers RC, Lee B, Prendergast RA. Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/MP-lpr/lpr mice. Cell Immunol 1992; 141: 496-507.
Jacob CO, McDevitt HO. Tumour necrosis factor-alpha in murine autoimmune ‘lupus’ nephritis. Nature 1988; 331: 356-358.
Jean FR, Daniel GF, Charles EW, Norman AG. Dietary phytoestrogens have anti-inflammatory activity in a guinea pig model of asthma. Proc Soc Exp Biol Med 2000; 223: 372-378.
Jevnikar AM, Grusby MJ, Glimcher LH. Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. J Exp Med 1994; 179: 1137-1143.
Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Biochem Soc Trans 2001; 31: 60-65.
Jones KL, Mansell A, Patella S, et al. Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. Proc Natl Acad Sci USA 2007; 104: 16239-16244.
Jung JI, Lim SS, Choi HJ, et al. Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. J Nutr Biochem 2006; 17: 689-696.
Kalkhoven E, Wissink S, van der Saag PT, van der Burg B. Negative interaction between the RelA(p65) subunit of NF-κB and the progesterone receptor. J Biol Chem 1996; 271: 6217-6224.
Kanda N, Tsuchida T, Tamaki K. Estrogen enhancement of anti-double stranded DNA antibody and immunoglobulin G production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 1999; 42: 328-337.
Kanauchi O, Serizawa I, Araki Y, et al. Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment. J Gastroenterol 2003; 38: 134-141.
Kang JL, Lee HW, Lee HS, et al. Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Respir Crit Care Med 2001; 164: 2206-2212.
Kasama T, Strieter RM, Lukacs NW, Lincoln PM, Burdick MD, Kunkel SL. Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 1995; 95: 2868-2876.
Katz RS, Holt-Daly N, MacDonald PA. Frequent infusion reactions associated with infliximab treatment in patients with polyarthritis related to systemic lupus erythematosus. Arthritis Rheum 2003; 48: S379.
Kiberd BA, Stadnyk AW. Established murine lupus nephritis does not respond to exogenous interleukin-1 receptor antagonist; a role for the endogenous molecule? Immunopharmacology 1995; 30: 131-137.
Kim BH, Chung EY, Ryu JC, Jung SH, Min KR, Kim Y. Anti-inflammatory mode of isoflavone glycoside sophoricoside by inhibition of interleukin-6 and cyclooxygenase-2 in inflammatory response. Arch Pharm Res 2003; 26: 306-311.
Kim SY, Shin HY, Lim JP, et al. Effects of Prunella vulgaris on mast cell-mediated allergic reaction and inflammatory cytokine production. Exp Biol Med 2007; 232: 921-926.
Kim YW, Zhao RJ, Park SJ, et al. Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol 2008; 154: 165-173.
Kincade PW, Medina KL, Smithson G, Scott DC. Pregnancy: a clue to normal regulation of B lymphopoiesis. Immunol Today 1994; 15: 539-544.
Kinghorn AD, Su BN, Jang DS, et al. Natural inhibitors of carcinogenesis. Planta Med 2004; 70: 691-705.
Kishimoto T, Taga T, Arkira S. Cytokine signal transduction. Cell 1994; 76: 253-262.
Kluger MJ. Fever: role of pyrogens and cryogens. Physiol Rev 1991; 71: 93-127.
Koehler KF, Helguero LA, Haldosén LA, Warner M, Gustafsson JA. Reflections on the discovery and significance of estrogen receptor beta. Endocr Rev 2005; 26: 465-478.
Kouro T, Medina KL, Oritani K, Kincade PW. Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators. Blood 2001; 97: 2708-2715
Kotzin B. Systemic lupus erythematosus. Cell 1996; 85(3): 303-306.
Krege JH, Hodgin JB, Couse JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA 1998; 95: 15677-15682.
Kuby K, Osborne, Goldsby. Leukocyte migration and inflammation. In Goldsby Ed., 4 ed., 2003; pp338-360: Freeman WH.
Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997; 138: 863-870.
Kwok BH, Koh B, Ndubuisi MI, Elofsson E, Crews CM. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 2001; 8: 759-766.
Kwon JM, Choi YJ, Choi JS, et al. Blockade of cytokine-induced endothelial cell adhesion molecule expression by licorice isoliquiritigenin through NF-κB signal disruption. Exp Biol Med 2007; 232: 235-245.
Lahita RG, Bradlow HL. Klinefelter''s syndrome: hormone metabolism in hypogonadal males with systemic lupus erythematosus. J Rheumatol Suppl 1987; 14: 154-157.
Lauener RPL, Goyert SM, Geha RS, Vercelli D. Interleukin-4 down-regulates the expression of CD14 in normal human monocytes. Eur J Immunol 1990; 20: 2375-2381.
Lauzurica P, Martinez-Martinez S, Marazuela M, et al. Pyrrolidine dithiocarbamate protects mice from lethal shock induced by LPS or TNF-α. Eur J Immunol 1999; l29: 1890-1900.
Lawrence T, Willoughby DA, Gilory DW. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol 2002; 2: 787-795.
Leiba A, Amital H, Gershwin ME, Shoenfeld. Diet and lupus. Lupus 2001; 10: 246-248.
Lemay S, Lebedeva TV, Singh AK. Inhibition of cytokine gene expression by sodium salicylate in a macrophage cell line through an NF-kappaB-independent mechanism. Clin Diagn Lab Immunol 1999; 6: 567-572.
Li J, McMurray RW. Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model. Clin Immunol 2007; 123: 219-226.
Liblau R, Tisch R, Bercovici N, McDevitt HO. Systemic antigen in the trearment of T-cell-mediated autoimmune disease. Immunology Today 1997; 18: 599-604.
Lim BO, Jolly CA, Zaman K, Fernandes G. Dietary (n-6) and (n-3) fatty acids and energy restriction modulate mesenteric lymph node lymphocyte function in autoimmune-prone (NZB×NZW) Fl mice. J Nutr 2000; 130: 1657-1664.
Lin BF, Jeng SJ, Chiano BL, Huang CC. Dietary fat affects lipids and anti-cardiolipin antibody levels in autoimmune-prone NZB/W F1 mice. Br J Nutr 1997; 77: 657-669.
Liu SF, Ye X, Malik AB. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes. Circulation 1999; 100: 1330-1337.
Llorente L, Richaud-Patin Y, Garcia-Padilla C, et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 2000; 43: 1790-1800.
Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 1993; 90: 11162-11166.
Ma J, Fu NY, Pang DB, Wu WY, Xu AL. Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. Planta Med 2001; 67: 754-757.
Macdougall IC, Cooper AC. Erythropoietin resistance: the role of inflammation and proinflammatory cytokines. Nephrol Dial Transplant 2002; 17 (Suppl) 11: 39-43.
Malinow MR, McLaughlin P, Stafford C, Livingston AL, Kohler GO. Alfalfa saponins and alfalfa seeds. Dietary effects in cholesterol-fed rabbits. Atherosclerosis 1980; 37: 433-438.
Malinow MR, Bardana EJ Jr, Pirofsky B, Craig S, McLaughlin P. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 1982; 216: 415-417.
Malinow MR, McLaughlin P, Bardana EJ Jr, Craig S. Elimination of toxicity from diets containing alfalfa seeds. Food Chem Toxicol 1984; 22: 583-587.
Manolios N, Schrieber L, Nelson M, Geczy CL. Enhanced interferon-gamma (IFN) production by lymph node cells from autoimmune (MRL/1, MRL/n) mice. Clin Exp Immunol 1989; 76: 301-306.
Masuzawa T, Miyaura C, Onoe Y, et al. Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow. J Clin Invest 1994; 94: 1090-1097.
McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuit M. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus 2001; 10: 779-783.
McHale JF, Harari OA, Marshall D, Haskard DO. TNFα and IL-1 sequentially induce endothelial ICAM-1 and VCAM-1 expression in MRL/lpr lupus-prone mice. J Immunol 1999; 163: 3993-4000.
Meisner M, Schmidt J, Schywalsky M, Tschaikowsky K. Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock. Int J Immunopharmacol 2000; 22: 83-90.
Mendlovic S, Brocke S, Shoenfeld Y, et al. Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype. Proc Natl Acad Sci USA 1988; 85: 2260-2264.
Mersereau JE, Levy N, Staub RE, et al. Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol Cel Endocrinol 2008; 283: 49-57.
Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1999; 16: 59-66.
Mohan AK, Edwards ET, Cote TR, Siegel JN, Braun MM. Drug-induced systemic lupus erythematosus and TNF-alpha blockers. Lancet 2002; 360: 646.
Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003; 56: 481-490.
Morimoto I, Shiozawa S, Tanaka Y, Fujita T. L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. Clin Immunol Immunopathol 1990; 55: 97-108.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348-2357.
Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996; 392: 49-53.
Mountz JD, Zhou T, Su X, Wu J, Cheng J. The role of programmed cell death as an emerging new concept for the pathogenesis of autoimmune diseases. Clin Immunol Immunopathol 1996; 80: S2-14.
Na SY, Kang BY, Chung SW, et al. Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NF-κB. J Biol Chem 1999; 274: 7674-7680.
Nathan CF. Secretory products of macrophages. J Clin Invest 1987; 79: 319-323.
Nagy G, Koncz A, Perl A. T- and B-cell abnormalities in systemic lupus erythematosus. Crit Rev Immunol 2005; 25: 123-140.
Nemeth ZH, Hasko G, Vizi ES. Pyrrolidine dithiocarbamate augments IL-10, inhibits TNF-α, MIP-1α, IL-12, and nitric oxide production and protects from the lethal effect of endotoxin. Shock 1998; 10: 49-53.
Neubauer BL, McNulty AM, Chedid M, et al. The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model. Cancer Res 2003; 63: 6056-6062.
Nilsson S, Makela S, Treuter E, et al. Mechanisms of estrogen action. Physiol Rev 2001; 81: 1535-1566.
Ohnishi K, Ebling FM, Mitchell B, Singh RR, Hahn BH, Tsao BP. Comparison of pathogenic and non-pathogenic murine antibodies to DNA: antigen binding and structural characteristics. Int Immunol 1994; 6: 817-830.
Okunade AL, Wiemer DF. (-)-Loliolide, an Ant-Repellent Compound from Xanthoxyllum setulosum. J Nat Prod 1985; 472-473.
Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996; 17: 369–384.
Paech K, Webb P, Kuiper GG, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP-1 sites. Science 1997; 277: 1508-1510.
Palmer E. Negative selection-clearing out the bar apples from the T cell repertoire. Nature Rev Immunol 2003; 3: 383-391.
Park YB, Lee SK, Kim DS, Lee J, Lee CH, Song CH. Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol. 1998; 16: 283-288.
Peng SL, Moslehi J, Craft J. Roles of interferon-g and interleukin-4 in murine lupus. J Clin Invest 1997; 99: 1936-1946.
Petri M. Diet and systemic lupus erythematosus: from mouse and monkey to woman? Lupus 2001; 10: 775-777.
Pine JW. Dubois’ lupus erythematosus. Editors, Wallace D. J. and Bevra H. H.; associated editors, Ouismorio J. R., Klinenberg 5th ed, 1997.
Pisetsky DS. Systemic lupus erythematosus. A. Epidemiology, pathology and pathogenesis. In: Klippel JH, ed. Primer on the Rheumatic Diseases, 11th ed. Georgia, USA: Arthritis Foundation, 1997: 246-251.
Powrie F, Leach MW. Genetic and spontaneous models of inflammatory bowel disease in rodents: evidence for abnormalities in mucosal immune regulation. Ther Immunol 1995; 2: 115-123.
Prud''homme GJ, Kono DH, Theofilopoulos AN. Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice. Mol Immunol 1995; 32: 495-503.
Quaedackers ME, Van Den Brink CE, Wissink S, et al. 4-hydroxytamoxifen trans-represses nuclear factor-κB activity in human osteoblastic U2-OS cells through estrogen receptor (ER)-α, and not through ER-β. Endocrinology 2001; 142: 1156-1166.
Quiring DP. Surface area determination. In: Glasser O (ed.) Medical Physics, vol 1. Chicago: Yearbook 1955; pp 1490-1494.
Raschke WC, Baird S, Ralph P, Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell 1978; 15: 261-267.
Reidenberg MM, Drayer DE, Lorenzo B, et al. Acetylation phenotypes and eniromental chemical exposure of people with idiopathic systemic lupus erythematosus. Arthritis Rheum 1993; 36: 971-973.
Rider V, Foster RT, Evans M, Suenaga R, Abdou NI. Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus. Clin Immunol Immunopathol 1998; 89: 171-180.
Reifen R, Blank M, Afek A, et al. Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus. Lupus 1998; 7: 192-197.
Roa R, Greenstein BD. Evidence for polymorphism of estrogen receptor capacity and affinity in liver and thymus of immature BALB/c and (NZBxNZW) F1 mice, a model of systemic lupus erythematosus. Int J Immunopharmacol 2000; 22: 897-903.
Robak E, Smolewski P, Wozniacka A, Sysa-Jedrzejowska A, Stepień H, Robak T. Relationship between peripheral blood dendritic cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cytokine Netw 2004; 15: 222-230.
Robak T, Gladalska A, R Stepień H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediators Inflamm 1998; 7: 347-353.
Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion. N Engl J Med 1983; 308: 1361.
Roitt I, Brostiff J, Male D. Cell migration and inflammation, In: Immunology, 6th ed., 2001; pp. 47-61, Mosby, London.
Ryffel B, Car BD, Gunn H, Roman D, Hiestand P, Mihatsch MJ. Interleukin-6 exacerbates glomerulonephritis in (NZB × NZW) F1 mice. Am J Pathol 1994; 144: 927-937.
Sadowska-Krowicka H, Mannick EE, Oliver PD, et al. Genistein and gut inflammation: role of nitric oxide. Proc Soc Exp Biol Med 1998; 217: 351-357.
Sanchez-Guerrero J, Karlson EW, Liang MH, Hunter DJ, Speizer FE, Colditz GA. Past use of oral contraceptives and the risk of developing systemic lupus erythematosus. Arthritis Rheum 1997; 40: 804-808.
Santiago-Raber ML, Laporte C, Reininger L, Izui S. Genetic basis of murine lupus. Autoimmun Rev 2004; 3: 33-39.
Swain SM, Armentano LE. Quantitative evaluation of fiber from nonforage sources used to replace alfalfa silage. J Dairy Sci 1994; 77: 2318-2331.
Schoenroth LJ, Hart DA, Pollard KM, Fritzler MJ. The effect of the phytoestrogen coumestrol on the NZB/W F1 murine model of systemic lupus. J Autoimmun 2004; 23: 323-332.
Schur PH. Genetics of systemic lupus erythematosus. Lupus 1995; 4: 425-437.
Seery JP, Carroll JM, Cattell V, Watt FM. Antinuclear autoantibodies and lupus nephritis in transgenic mice expressing interferon-gamma in the epidermis. J Exp Med 1997; 186: 1451-1459.
Seery JP. IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus? Arthritis Res 2000; 2: 437-440.
Segal R, Dayan M, Zinger H, Mozes E. Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline. Lupus 2001; 10: 23-31.
Schreiber RD, Hicks LJ, Celada A, Buchmeier NA, Gray PW. Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol 1985; 134: 1609-1618.
Shim GJ, Wang L, Andersson S,et al. Disruption of the estrogen receptor ß gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis. Proc Natl Acad Sci USA 2003; 100: 6694-6699.
Shim GJ, Kis LL, Warner M, Gustafsson JA. Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor α gene. Proc Natl Acad Sci USA 2004; 101: 1720-1724.
Shim GJ, Warner M, Kim HJ, et al. Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren’s syndrome. Proc Natl Acad Sci USA 2004; 101: 12628-12633.
Shirai A, Conover J, Klinman DM. Increased activation and altered ratio of interferon-gamma: interleukin-4 secreting cells in MRL-lpr/lpr mice. Autoimmunity 1995; 21: 107-116.
Shoenfeld Y, Krause I, Blank M. New methods of treatment in an experimental murine model of systemic lupus erythematosus induced by idiotypic manipulation. Ann Rheum Dis 1997; 56: 5-11.
Silfen SL, Ciaccia AV, Bryant HU. Selective estrogen receptor modulators: tissue selectivity and differential uterine effects. Climacteric 1999; 2: 268-283.
Steinberg FM, Guthrie NL, Villablanca AC, Kumar K, Murray MJ. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr 2003; 78: 123-130.
Story JA, LePage SL, Petro MS, et al. Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats. Am J Clin Nutr 1984; 39: 917-929.
Sthoeger ZM, Zinger H, Mozes E. Beneficial effects of the anti-oestrogen tamoxifen on systemic lupus erythematosus of NZB/W F1 female mice are associated with specific reduction of IgG3 autoantibodies. Ann Rheum Dis 2003; 62: 341-346.
Strom A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson JA. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line. Proc Natl Acad Sci USA 2004; 101: 1566-1571.
Sugiyama M, Funauchi M, Yamagata T, et al. Predominant inhibition of Th1 cytokines in New Zealand black/white F1 mice treated with FK506. Scand J Rheumatol 2004; 33: 108-114.
Suzuki H, Yasukawa K, Saito T, et al. Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. Eur J Immunol 1993; 23: 1078-1082.
Takahashi S, Fossati L, Lwamoto M, et al. Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. J Clin Invest 1996; 97: 1597-1604.
Takano H, Osakabe N, Sanbongi C, et al. Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Exp Biol Med 2004; 229: 247-254.
Takayama K, Qureshi N. Chemical structure of lipid A. In “Molecular Biochemistry and Cellular Biology” , eds by Morrison DC, Ryan JL. 1992; 1: 43-60.
Takemura T, Yoshioka K, Murakami K, et al. Cellular localization of inflammatory cytokines in human glomerulonephritis. Virchows Arch 1994; 424: 459-464.
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277.
Tang B, Matsuda T, Akira S, et al. Age associated increase in interleukin 6 in MRL/lpr mice. Int Immunol 1991; 3: 273-278.
Tsai CY, Wu TH, Huang SF, et al. Abnormal splenic and thymic IL-4 and TNF-α expression in MRL-lpr/lpr mice. Scand J Immunol 1995; 41: 157-163.
Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol 1985; 37: 269-390
Theofilopoulos AN, Singer PA, Kofler R, Kono DH, Duchosal MA, Balderas RS. B and T cell antigen receptor repertoires in lupus/arthritis murine models. Springer Semin Immunopathol 1989; 11: 457-469.
Thurmond TS, Murante FG, Staples JE, Silverstone AE, Korach KS, Gasiewicz TA. Role of estrogen receptor alpha in hematopoietic stem cell development and B lymphocyte maturation in the male mouse. Endocrinology 2000; 141: 2309-2318.
Trompezinski S, Denis A, Schmitt D, Viac J. Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFalpha. Arch Dermatol Res 2003; 295: 112-116.
Troyer DA, Chandrasekar B, Barnes JL, Fernandes G. Calorie restriction decreases platelet-derived growth factor (PDGF)-A and thrombin receptor mRNA expression in autoimmune murine lupus nephritis. Clin Exp Immunol 1997; 108: 58-62.
Tuscano JM, Hsu TC, McKnight H, Ansari AA, Gershwin ME. Phosphorylation abnormalities: NZB mice exhibit a B-cell signaling defect. J Autoimmunity 2002; 19: 103-109.
Ueda H, Yamazaki M. Anti-inflammatory and anti-allergic actions by oral administration of a perilla leaf extract in mice. Biosci Biotechnol Biochem 2001; 65: 1673-1675.
Wagner JD, Schwenke DC, Greaves KA, et al. Soy protein with isoflavones, but not an isoflavone-rich supplement, improves arterial low-density lipoprotein metabolism and atherogenesis. Arterioscler Thromb Vasc Biol 2003; 23: 2241-2246.
Walter P, Green S, Greene G, et al. Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci USA 1985; 82: 7889-7893.
Wan JM, Sit WH, Lee CL, Fu KH, Chan DK. Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury. Int Immunopharmacol 2006; 6: 750-758.
Ward HW. Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J 1973; 1: 13-14.
Warner LM, Adams LM, Sehgal SN. Rapamycin prolongs survival and arrests pathophysiologic changes in murine systemic lupus erythematosus. Arthritis Rheum 1994; 37: 289-297.
Wang C, Fu M, Angeletti RH, et al. Direct acetylation of the estrogen receptor-α hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem 2001; 276: 18375-18383.
Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 1992; 356: 314-317.
Weidler C, Harle P, Schedel J, Schmidt M, Scholmerich J, Straub RH. Patients with rheumatoid arthritis and systemic lupus erythematosus have increased renal excretion of mitogenic estrogens in relation to endogenous antiestrogens. J Rheumatol 2004; 31: 489-494.
Whittam J, Jensen C, Hudson T. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr 1995; 62: 1025-1026.
Wu WM, Suen JL, Lin BF, Chiang BL. Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice. Immunology 2000a; 100: 110-118.
Wu WM, Lin BF, Su YC, Suen JL, Chiang BL. Tamoxifen decreases renal Inflammation and alleviates disease severity in autoimmune NZB/W F1 mice. Scand J Immunol 2000b; 52: 393-400.
Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther 2001; 296: 181-187.
Yamamoto S, Aizu E, Jiang H, et al. The potent anti-tumor-promoting agent. Isoliquiritigenin. Carcinogenesis 1991 12: 317-323.
Yang F, Villiers W, McClain C, Varilek G. Green tea polyphenols block endotoxin-induced tumor necrosis factor production and lethality in a murine model. J Nutr 1998; 128: 2334-2340.
Ye YL, Suen JL, Chen YY, Chiang BL. Phenotypic and functional analysis of activated B cells of autoimmune NZB/W F1 mice. Scand J Immunol 1998; 47: 122-126.
Yellayi S, Naaz A, Szewczykowski MA, et al. The phytoestrogen genistein induces thymic and immune changes: a human health concern? Proc Natl Acad Sci USA 2002; 99: 7616-7621.
Yellayi S, Zakroczymski MA, Selvaraj V, et al. The phytoestrogen genistein suppresses cellmediated immunity in mice. J Endocrinol 2003; 176: 267-274.
Yin Z, Bahtiyar G, Zhang N, et al. IL-10 regulates murine lupus. J Immunol 2002; 169: 2148-2155.
Zavala F, Masson A, Hadaya K, et al. Granulocyte-colony stimulating factor treatment of lupus autoimmune disease in MRL-lpr/lpr mice. J Immunol 1999; 163: 5125-5132.
Zhao JH, Arao Y, Sun SJ, Kikuchi A, Kayama F. Oral administration of soy-derived genistin suppresses lipopolysaccharide-induced acute liver inflammation but does not induce thymic atrophy in the rat. Life Sci 2006; 78: 812-819.
Zuckerman SH, Bryan-Poole N. Estrogen-induced alterations in lipoprotein metabolism in autoimmune MRL/lpr mice. Arterioscler Thromb Vasc Biol 1995; 15: 1556-1562.
Zuckerman SH, Ahmari SE, Bryan-Poole N, Evans GF, Short L, Glasebrook AL. Estriol: a potent regulator of TNF and IL-6 expression in a murine model of endotoxemia. Inflammation 1996; 20: 581-597.