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研究生:洪竹瑩
研究生(外文):Jhu-ying Hong
論文名稱:海洋衍生物之修飾物對於異位性皮膚炎的調節作用
論文名稱(外文):Modulation of atopic dermatitis by modifying marine-derived compound
指導教授:指導教授
指導教授(外文):溫志宏
學位類別:碩士
校院名稱:國立中山大學
系所名稱:海洋生物科技暨資源學系研究所
學門:自然科學學門
學類:海洋科學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:112
中文關鍵詞:抗血管新生抗氧化壓力抗發炎異位性皮膚炎
外文關鍵詞:anti-inflammationanti-angiogenesisanti-oxidationAtopic dermatitis
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異位性皮膚炎是一常見慢性發炎性皮膚疾病。雖然目前異位性皮膚炎發病機制尚不明確,但有許多研究認為異位性皮膚炎主要是由遺傳問題、環境因子、免疫失調以及皮膚屏障功能缺失所造成。除了發炎以外,血管新生以及氧化壓力同樣也參與異位性皮膚炎的病程並扮演著重要角色。至今,異位性皮膚炎治療用藥並無法完全治癒疾病且伴隨許多副作用產生。因此找尋一個能夠有效治療異位性皮膚炎的藥物是急迫需要的。許多海洋化合物被報導其生物活性具有抗腫瘤、抗發炎以及抗過敏等功效,而這些海洋化合物所擁有的生物活性可能成為發展新型異位性皮膚炎用藥的潛力物質。WH-4是一個合成軟珊瑚天然物之中間類似物購自商業公司。本研究中利用巨噬細胞RAW264.7作為離體模式檢測WH-4抗發炎以及抗氧化壓力的能力。在活體模式中使用轉殖型基因螢光蛋白斑馬魚檢測WH-4在血管新生中的效用。最後運用在異位性皮膚炎小鼠模式以檢測WH-4對於異位性皮膚炎的效用。實驗結果得知,本研究發現WH-4具有抗發炎、抗氧化壓力以及抗血管新生的功能。同樣的WH-4在異位性小鼠模式中可以降低因發炎、氧化壓力以及血管新生所造成的傷口。由以上實驗結果我們認為WH-4可能成為異位性皮膚炎的潛力用藥。
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Although the detailed mechanisms of AD remain unclear, some studies indicated that genetic predisposition, environmental factors, immunological mechanisms and skin barrier dysfunction may cause AD mainly. On the other hand, AD is characterized by angiogenesis and oxidative stress which is major diagnostic criteria. Today, AD treatment could not totally cure AD but also have many side effect. Therefore, finding more effective drugs for AD is pressing need. Numbers of marine compounds were reported for their bioactivities such as anti-tumor, anti-inflammation and anti-allergy. WH-4 is a synthesized coral related compound obtained from commercial company. In our study, we used in vitro study to detect anti-inflammatory and anti-oxidation ability in RAW264.7, in vivo study we used Tg(fli1a:EGFP)y1 zebrafish to examine the antiangiogenic effect of WH-4. In addition, we also used mice model of AD to examine the effect of WH-4 on AD. In our result, we found that WH-4 had anti-inflammation, anti-oxidation and anti-angiogenesis activity. Also WH-4 could reduce the severity in AD mice model resulted from reducing inflammation, oxidative stress and angiogenesis. Based on above results, we demonstrate that WH-4 may be a potential drug for AD.
第一章、 前言 1
1.1 異位性皮膚炎流行病學之介紹 1
1.2 異位性皮膚炎之臨床特點及診斷方式 2
1.3 異位性皮膚炎致病因素 5
1.4 發炎在異位性皮膚炎所扮演之角色 5
1.5 巨噬細胞在異位性皮膚炎之關聯 9
1.6 氧化壓力與異位性皮膚炎之關聯 11
1.7 血管新生在異位性皮膚炎上之角色 13
1.8 現今臨床異位性皮膚炎用藥 17
1.8.1 局部皮質類固醇 (topical corticosteroids, TCSs) 18
1.8.2 局部鈣調磷酸酶抑制劑 (topical calcineurin inhibitors, TCIs) 19
1.9 異位性皮膚炎之實驗模式 21
1.10 海洋在藥物開發上之優勢 22
1.11 研究目的與動機 25
第二章、 材料與方法 27
2.1 離體細胞模式 27
2.1.1 細胞選用及藥物來源 27
2.1.2 細胞存活率測試 27
2.1.3 離體抗發炎模式 28
2.1.4 實驗分組 28
2.1.5 細胞蛋白質分析與西方墨點法 28
2.2 動物模式 29
2.2.1 動物照護 29
2.2.2 動物誘發模式 30
2.2.3 傷口給藥 30
2.2.4 傷口觀察 30
2.2.5 實驗分組&實驗流程圖 30
2.2.6 皮膚樣品蒐集與組織學分析 31
2.2.7 免疫組織化學染色 32
2.2.8 使用之目標抗體 34
2.2.9 組織前處理及蛋白質分析與西方墨點法 35
2.2.10 斑馬魚種及飼養條件 36
2.2.11 斑馬魚交配與胚胎培養 36
2.2.12 斑馬魚胚胎存活率測試 36
2.2.13 斑馬魚體節間血管新生 37
2.3 實驗數據分析 37
第三章、 實驗結果 38
3.1 細胞實驗結果 38
3.1.1 WH-4對老鼠巨噬細胞株RAW264.7存活率影響 38
3.1.2 WH-4對於LPS誘發老鼠巨噬細胞株RAW264.7發炎因子表現 38
3.1.2.1 WH-4對LPS誘發老鼠巨噬細胞株RAW264.7發炎性蛋白iNOS之影響 38
3.1.2.2 WH-4對LPS誘發老鼠巨噬細胞株RAW264.7發炎性蛋白COX-2之影響 39
3.1.3 WH-4對於LPS誘發老鼠巨噬細胞株RAW264.7抗氧化壓力蛋白HO-1表現量之影響 39
3.2 動物實驗結果 39
3.2.1 WH-4對斑馬魚 (AB strain Danio rerior) 胚胎存活率之影響 39
3.2.2 WH-4對Tg(fli1:EGFP)螢光斑馬魚仔魚之體節間血管(intersegmental vessel, ISV) 生成之影響 40
3.2.3 WH-4對於異位性皮膚炎 (atopic dermatitis, AD) 傷口外觀之影響 40
3.2.4 WH-4對於AD皮膚組織病理組織切片之影響 41
3.2.4.1 WH-4對於AD表皮不當增生之影響 41
3.2.4.2 WH-4對於AD免疫細胞浸潤程度之影響 41
3.2.5 WH-4對於AD皮膚組織中輔助性T細胞 (Th cell) 浸潤之影響 42
3.2.6 WH-4對於AD皮膚組織中IFN-表現之影響 42
3.2.7 WH-4對於AD皮膚組織中發炎蛋白質表現之影響 43
3.2.7.1 WH-4對於AD皮膚組織中發炎性蛋白iNOS表現量之影響 43
3.2.7.2 WH-4對於AD皮膚組織中發炎性蛋白COX-2表現量之影響 43
3.2.8 WH-4對於AD皮膚組織中抗氧化壓力蛋白HO-1表現之影響 43
3.2.9 WH-4對於AD皮膚組織中血管新生相關蛋白表現之影響 44
3.2.9.1 WH-4對於AD皮膚組織中血管新生相關蛋白VEGF-A表現量之影響 44
3.2.9.2 WH-4對於AD皮膚組織中血管新生相關蛋白CD31表現量之影響 44
3.2.9.3 WH-4對於AD皮膚組織中血管新生相關蛋白vWF表現量之影響 44
第四章、 討論 64
4.1 巨噬細胞在發炎中扮演的角色 65
4.2 發炎與氧化壓力的關係 66
4.3 發炎與血管新生的關係 67
4.4 發炎與異位性皮膚炎 70
4.4.1 WH-4對於BALB/c小鼠異位性皮膚炎之傷口外觀評分 70
4.4.2 WH-4對於BALB/c小鼠異位性皮膚炎之病理組織切片分析 71
4.4.3 異位性皮膚炎與Th1細胞及IFN-之關聯 72
4.4.4 巨噬細胞在異位性皮膚炎中扮演的角色 73
4.5 異位性皮膚炎與氧化壓力 75
4.6 異位性皮膚炎與血管新生之關係 76
第五章 未來展望 79
第六章 文獻參考 81
1.Bieber, T., Atopic dermatitis. Ann Dermatol, 2010. 22(2): p. 125-37.
2.Nutten, S., Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab, 2015. 66 Suppl 1: p. 8-16.
3.Watson, W. and S. Kapur, Atopic dermatitis. Allergy Asthma Clin Immunol, 2011. 7 Suppl 1: p. S4.
4.Lewis-Jones, S., Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract, 2006. 60(8): p. 984-92.
5.Chamlin, S.L., et al., Effects of atopic dermatitis on young American children and their families. Pediatrics, 2004. 114(3): p. 607-11.
6.Charman, C.R., A.D. Morris, and H.C. Williams, Topical corticosteroid phobia in patients with atopic eczema. Br J Dermatol, 2000. 142(5): p. 931-6.
7.Hanifin, J.M., et al., Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association "Administrative Regulations for Evidence-Based Clinical Practice Guidelines". J Am Acad Dermatol, 2004. 50(3): p. 391-404.
8.Williams, H.C., Clinical practice. Atopic dermatitis. N Engl J Med, 2005. 352(22): p. 2314-24.
9.Lapidus, C.S., D.F. Schwarz, and P.J. Honig, Atopic dermatitis in children: who cares? Who pays? J Am Acad Dermatol, 1993. 28(5 Pt 1): p. 699-703.
10.Ellis, C.N., et al., Cost of atopic dermatitis and eczema in the United States. J Am Acad Dermatol, 2002. 46(3): p. 361-70.
11.Drucker, A.M., et al., The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol, 2017. 137(1): p. 26-30.
12.Goyal, T., Atopic dermatitis and tacrolimus: Current perspectives. Indian Journal of Paediatric Dermatology, 2013. 14(3): p. 54-61.
13.Lebwohl, M.G., et al., Pathways to managing atopic dermatitis: consensus from the experts. J Clin Aesthet Dermatol, 2013. 6(7 Suppl): p. S2-S18.
14.Thomsen, S.F., Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy, 2014. 2014: p. 354250.
15.Kim, J.E., et al., Consensus Guidelines for the Treatment of Atopic Dermatitis in Korea (Part II): Systemic Treatment. Ann Dermatol, 2015. 27(5): p. 578-92.
16.Hanifin, J.M., et al., The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol, 2001. 10(1): p. 11-8.
17.Lim, H.S., et al., Morus alba L. suppresses the development of atopic dermatitis induced by the house dust mite in NC/Nga mice. BMC Complement Altern Med, 2014. 14: p. 139.
18.Hwang, J.S., et al., Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis. BMC Complement Altern Med, 2012. 12: p. 159.
19.Yang, I.J., D.U. Lee, and H.M. Shin, Inhibitory Effect of Valencene on the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice. Evid Based Complement Alternat Med, 2016. 2016: p. 9370893.
20.Elias, P.M. and M. Steinhoff, "Outside-to-inside" (and now back to "outside") pathogenic mechanisms in atopic dermatitis. J Invest Dermatol, 2008. 128(5): p. 1067-70.
21.Nedoszytko, B., et al., Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: atopic dermatitis, psoriasis and skin mastocytosis. Postepy Dermatol Alergol, 2014. 31(2): p. 84-91.
22.Noel Vinay Thomas., S.-K.K., Potential Cosmeceutical Applications of Phlorotannins and Fucoidans from Marine Algae in the Treatment of Atopic Dermatitis. Marine Cosmeceuticals, 2011: p. 257-266.
23.Lee, S.H., Y. Heo, and Y.C. Kim, Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J Vet Sci, 2010. 11(1): p. 35-41.
24.Chung, T.H., et al., Effectiveness of the Novel Herbal Medicine, KIOM-MA, and Its Bioconversion Product, KIOM-MA128, on the Treatment of Atopic Dermatitis. Evid Based Complement Alternat Med, 2012. 2012: p. 762918.
25.山東哲夫, 李.劉., 異位性皮膚炎的診斷與治療. 1 ed. 2000: 白象文化事業有限公司.
26.Grewe, M., et al., A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today, 1998. 19(8): p. 359-61.
27.Leung, D.Y. and N.A. Soter, Cellular and immunologic mechanisms in atopic dermatitis. J Am Acad Dermatol, 2001. 44(1 Suppl): p. S1-S12.
28.Kim, K.H., Overview of atopic dermatitis. Asia Pac Allergy, 2013. 3(2): p. 79-87.
29.Zhu, J., H. Yamane, and W.E. Paul, Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol, 2010. 28: p. 445-89.
30.Zhu, J. and W.E. Paul, CD4 T cells: fates, functions, and faults. Blood, 2008. 112(5): p. 1557-69.
31.Raphael, I., et al., T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine, 2015. 74(1): p. 5-17.
32.Koga, C., et al., Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol, 2008. 128(11): p. 2625-30.
33.Herz, U., R. Bunikowski, and H. Renz, Role of T cells in atopic dermatitis. New aspects on the dynamics of cytokine production and the contribution of bacterial superantigens. Int Arch Allergy Immunol, 1998. 115(3): p. 179-90.
34.Skurkovich, S. and B. Skurkovich, Anticytokine therapy, especially anti-interferon-gamma, as a pathogenetic treatment in TH-1 autoimmune diseases. Ann N Y Acad Sci, 2005. 1051: p. 684-700.
35.Bosisio, D., et al., Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood, 2002. 99(9): p. 3427-31.
36.Schroder, K., et al., Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 2004. 75(2): p. 163-89.
37.Vahedi, G., et al., Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol Rev, 2013. 252(1): p. 24-40.
38.Berger, A., Th1 and Th2 responses: what are they? BMJ, 2000. 321(7258): p. 424.
39.Park, H., et al., A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol, 2005. 6(11): p. 1133-41.
40.Hori, S., T. Nomura, and S. Sakaguchi, Control of regulatory T cell development by the transcription factor Foxp3. Science, 2003. 299(5609): p. 1057-61.
41.Tan, C. and I. Gery, The unique features of Th9 cells and their products. Crit Rev Immunol, 2012. 32(1): p. 1-10.
42.Kaplan, M.H., Th9 cells: differentiation and disease. Immunol Rev, 2013. 252(1): p. 104-15.
43.Duhen, T., et al., Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol, 2009. 10(8): p. 857-63.
44.Nograles, K.E., et al., IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol, 2009. 123(6): p. 1244-52 e2.
45.Grewe, M., et al., Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J Invest Dermatol, 1995. 105(3): p. 407-10.
46.Biedermann, T., et al., Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang of Cutaneous Inflammation. Front Immunol, 2015. 6: p. 353.
47.Spergel, J.M., et al., Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest, 1999. 103(8): p. 1103-11.
48.Simon, D., et al., Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment. Allergy, 2005. 60(7): p. 944-51.
49.Fiset, P.O., D.Y. Leung, and Q. Hamid, Immunopathology of atopic dermatitis. J Allergy Clin Immunol, 2006. 118(1): p. 287-90.
50.Gajewski, T.F., E. Goldwasser, and F.W. Fitch, Anti-proliferative effect of IFN-gamma in immune regulation. II. IFN-gamma inhibits the proliferation of murine bone marrow cells stimulated with IL-3, IL-4, or granulocyte-macrophage colony-stimulating factor. J Immunol, 1988. 141(8): p. 2635-42.
51.Grewe, M., et al., Lesional expression of interferon-gamma in atopic eczema. Lancet, 1994. 343(8888): p. 25-6.
52.Biedermann, T., M. Rocken, and J.M. Carballido, TH1 and TH2 lymphocyte development and regulation of TH cell-mediated immune responses of the skin. J Investig Dermatol Symp Proc, 2004. 9(1): p. 5-14.
53.Aderem, A. and R.J. Ulevitch, Toll-like receptors in the induction of the innate immune response. Nature, 2000. 406(6797): p. 782-7.
54.Park, E.J., et al., Effect of topical application of quercetin-3-O-(2''-gallate)-alpha-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice. J Dermatol Sci, 2015. 77(3): p. 166-72.
55.Kiekens RC, T.T., Oosting AJ, Bihari IC, Van De Winkel JG, Bruijnzeel-Koomen CA, Knol EF., Heterogeneity within tissue-specific macrophage and dendritic cell populations during cutaneous inflammation in atopic dermatitis. Br J Dermatol. , 2001: p. 957-965.
56.Kasraie, S. and T. Werfel, Role of macrophages in the pathogenesis of atopic dermatitis. Mediators Inflamm, 2013. 2013: p. 942375.
57.Boguniewicz, M. and D.Y. Leung, 10. Atopic dermatitis. J Allergy Clin Immunol, 2006. 117(2 Suppl Mini-Primer): p. S475-80.
58.McNeill, E., et al., Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation. Free Radic Biol Med, 2015. 79: p. 206-16.
59.Liaudet, L., F.G. Soriano, and C. Szabo, Biology of nitric oxide signaling. Crit Care Med, 2000. 28(4 Suppl): p. N37-52.
60.Laouini, D., et al., COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization. J Allergy Clin Immunol, 2005. 116(2): p. 390-6.
61.Orita, K., et al., Inducible nitric oxide synthase (iNOS) and alpha-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice. Exp Dermatol, 2011. 20(11): p. 911-4.
62.Taniuchi, S., et al., Increased serum nitrate levels in infants with atopic dermatitis. Allergy, 2001. 56(7): p. 693-5.
63.Fogh, K., T. Herlin, and K. Kragballe, Eicosanoids in skin of patients with atopic dermatitis: prostaglandin E2 and leukotriene B4 are present in biologically active concentrations. J Allergy Clin Immunol, 1989. 83(2 Pt 1): p. 450-5.
64.Choi, Y.H., G.Y. Kim, and H.H. Lee, Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-kappaB signaling pathways. Drug Des Devel Ther, 2014. 8: p. 1941-53.
65.Fujiwara, N. and K. Kobayashi, Macrophages in inflammation. Curr Drug Targets Inflamm Allergy, 2005. 4(3): p. 281-6.
66.Tseng, C.K., et al., Aqueous extract of Gracilaria tenuistipitata suppresses LPS-induced NF-kappaB and MAPK activation in RAW 264.7 and rat peritoneal macrophages and exerts hepatoprotective effects on carbon tetrachloride-treated rat. PLoS One, 2014. 9(1): p. e86557.
67.Lin, H.Y., et al., Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. Biochem Pharmacol, 2003. 66(9): p. 1821-32.
68.Lee, S.J., et al., Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation. Mol Cells, 2003. 16(1): p. 97-105.
69.Anwar, M.A., S. Basith, and S. Choi, Negative regulatory approaches to the attenuation of Toll-like receptor signaling. Exp Mol Med, 2013. 45: p. e11.
70.Chiara Castellini, S.B., Paolo Govoni, Stefano Guizzardi, Anti Inflammatory Property of PDRN—An in Vitro Study on Cultured Macrophages. Advances in Bioscience and Biotechnology, 2017.
71.Choi, E.M. and J.K. Hwang, Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages. Fitoterapia, 2005. 76(7-8): p. 608-13.
72.Lee, H.N., et al., Mechanisms by which licochalcone e exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and lipopolysaccharide-stimulated murine macrophages. Int J Mol Sci, 2013. 14(6): p. 10926-43.
73.Su-Jin Kim, J.-H.L., Chung Hwan Oh, Sa-Rang Oh and Ji-Wook Jung, Chungyangeum Attenuated the Allergic Inflammation in vivo and in vitro. Biomedical Science Letters, 2013: p. 285~294.
74.Ahn, K.S., et al., Inhibition of inducible nitric oxide synthase and cyclooxygenase II by Platycodon grandiflorum saponins via suppression of nuclear factor-kappaB activation in RAW 264.7 cells. Life Sci, 2005. 76(20): p. 2315-28.
75.Park, S.J., et al., Platycodon grandiflorus alleviates DNCB-induced atopy-like dermatitis in NC/Nga mice. Indian J Pharmacol, 2012. 44(4): p. 469-74.
76.Kang, N.J., et al., Diphlorethohydroxycarmalol inhibits interleukin-6 production by regulating NF-kappaB, STAT5 and SOCS1 in lipopolysaccharide-stimulated RAW264.7 cells. Mar Drugs, 2015. 13(4): p. 2141-57.
77.Chun, J., A. Tosun, and Y.S. Kim, Anti-inflammatory effect of corymbocoumarin from Seseli gummiferum subsp. corymbosum through suppression of NF-kappaB signaling pathway and induction of HO-1 expression in LPS-stimulated RAW 264.7 cells. Int Immunopharmacol, 2016. 31: p. 207-15.
78.Bowler, R.P. and J.D. Crapo, Oxidative stress in allergic respiratory diseases. J Allergy Clin Immunol, 2002. 110(3): p. 349-56.
79.Tsukahara, H., et al., Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis. Life Sci, 2003. 72(22): p. 2509-16.
80.Otterbein, L.E., et al., Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol, 2003. 24(8): p. 449-55.
81.Araujo, J.A., M. Zhang, and F. Yin, Heme oxygenase-1, oxidation, inflammation, and atherosclerosis. Front Pharmacol, 2012. 3: p. 119.
82.Wagener, F.A., et al., Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression. J Pharmacol Exp Ther, 1999. 291(1): p. 416-23.
83.Choi, A.M. and J. Alam, Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol, 1996. 15(1): p. 9-19.
84.Maines, M.D., Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J, 1988. 2(10): p. 2557-68.
85.Paine, A., et al., Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol, 2010. 80(12): p. 1895-903.
86.Lee, J., et al., Heme oxygenase-1-mediated anti-inflammatory effects of tussilagonone on macrophages and 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation in mice. Int Immunopharmacol, 2016. 34: p. 155-64.
87.Kirino, M., et al., Heme oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice: implications for human disease. J Allergy Clin Immunol, 2008. 122(2): p. 290-7, 297 e1-8.
88.Listopad, J., et al., Heme oxygenase-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells. Exp Dermatol, 2007. 16(8): p. 661-70.
89.Lee, T.S. and L.Y. Chau, Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med, 2002. 8(3): p. 240-6.
90.Kirino, Y., et al., Tumor necrosis factor alpha acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytes. Arthritis Rheum, 2007. 56(2): p. 464-75.
91.Udono-Fujimori, R., et al., Expression of heme oxygenase-1 is repressed by interferon-gamma and induced by hypoxia in human retinal pigment epithelial cells. Eur J Biochem, 2004. 271(14): p. 3076-84.
92.Pae, H.O., et al., Heme oxygenase-1 attenuates contact hypersensitivity induced by 2,4-dinitrofluorobenzene in mice. Immunopharmacol Immunotoxicol, 2008. 30(2): p. 207-16.
93.Varricchi, G., et al., Angiogenesis and lymphangiogenesis in inflammatory skin disorders. J Am Acad Dermatol, 2015. 73(1): p. 144-53.
94.Zgraggen, S., A.M. Ochsenbein, and M. Detmar, An important role of blood and lymphatic vessels in inflammation and allergy. J Allergy (Cairo), 2013. 2013: p. 672381.
95.Szekanecz, Z. and A.E. Koch, Mechanisms of Disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol, 2007. 3(11): p. 635-43.
96.Jackson, J.R., et al., The codependence of angiogenesis and chronic inflammation. FASEB J, 1997. 11(6): p. 457-65.
97.Schonthaler, H.B., et al., Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis. Proc Natl Acad Sci U S A, 2009. 106(50): p. 21264-9.
98.Steinhoff, M., et al., Role of vasculature in atopic dermatitis. J Allergy Clin Immunol, 2006. 118(1): p. 190-7.
99.Samochocki, Z., et al., Expression of vascular endothelial growth factor and other cytokines in atopic dermatitis, and correlation with clinical features. Int J Dermatol, 2016. 55(3): p. e141-6.
100.Jung, M.K., et al., Tannic acid and quercetin display a therapeutic effect in atopic dermatitis via suppression of angiogenesis and TARC expression in Nc/Nga mice. J Invest Dermatol, 2010. 130(5): p. 1459-63.
101.Zhang, Y., H. Matsuo, and E. Morita, Increased production of vascular endothelial growth factor in the lesions of atopic dermatitis. Arch Dermatol Res, 2006. 297(9): p. 425-9.
102.Hussain, Z., et al., Efficient immuno-modulation of TH1/TH2 biomarkers in 2,4-dinitrofluorobenzene-induced atopic dermatitis: nanocarrier-mediated transcutaneous co-delivery of anti-inflammatory and antioxidant drugs. PLoS One, 2014. 9(11): p. e113143.
103.Genovese, A., et al., Angiogenesis, lymphangiogenesis and atopic dermatitis. Chem Immunol Allergy, 2012. 96: p. 50-60.
104.Chen, L., et al., The progression of inflammation parallels the dermal angiogenesis in a keratin 14 IL-4-transgenic model of atopic dermatitis. Microcirculation, 2008. 15(1): p. 49-64.
105.Voskas, D., et al., An eosinophil immune response characterizes the inflammatory skin disease observed in Tie-2 transgenic mice. J Leukoc Biol, 2008. 84(1): p. 59-67.
106.Puxeddu, I., et al., Human peripheral blood eosinophils induce angiogenesis. Int J Biochem Cell Biol, 2005. 37(3): p. 628-36.
107.Kawakami, T., et al., Mast cells in atopic dermatitis. Curr Opin Immunol, 2009. 21(6): p. 666-78.
108.Detoraki, A., et al., Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects. J Allergy Clin Immunol, 2009. 123(5): p. 1142-9, 1149 e1-5.
109.Marone, G., et al., Role of human mast cells and basophils in bronchial asthma. Adv Immunol, 2005. 88: p. 97-160.
110.Leung, D.Y. and T. Bieber, Atopic dermatitis. Lancet, 2003. 361(9352): p. 151-60.
111.Granata, F., et al., Production of vascular endothelial growth factors from human lung macrophages induced by group IIA and group X secreted phospholipases A2. J Immunol, 2010. 184(9): p. 5232-41.
112.Corliss, B.A., et al., Macrophages: An Inflammatory Link Between Angiogenesis and Lymphangiogenesis. Microcirculation, 2016. 23(2): p. 95-121.
113.Costa, C., et al., Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol, 2002. 55(6): p. 429-34.
114.Xiong, M., et al., Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway. Am J Pathol, 1998. 153(2): p. 587-98.
115.Leibovich, S.J., et al., Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci U S A, 1994. 91(10): p. 4190-4.
116.Park, C.Y., et al., Cyclooxygenase-2-expressing macrophages in human pterygium co-express vascular endothelial growth factor. Mol Vis, 2011. 17: p. 3468-80.
117.Kuwano, T., et al., Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J, 2004. 18(2): p. 300-10.
118.Mollace, V., et al., Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacol Rev, 2005. 57(2): p. 217-52.
119.Lamon, B.D., et al., Inducible nitric oxide synthase gene deletion exaggerates MAPK-mediated cyclooxygenase-2 induction by inflammatory stimuli. Am J Physiol Heart Circ Physiol, 2010. 299(3): p. H613-23.
120.Puxeddu, I., et al., The role of eosinophil major basic protein in angiogenesis. Allergy, 2009. 64(3): p. 368-74.
121.Nissim Ben Efraim, A.H. and F. Levi-Schaffer, Roles of eosinophils in the modulation of angiogenesis. Chem Immunol Allergy, 2014. 99: p. 138-54.
122.Berman, M.E., Y. Xie, and W.A. Muller, Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural killer cell transendothelial migration and beta 2 integrin activation. J Immunol, 1996. 156(4): p. 1515-24.
123.Wang, D., et al., Immunohistochemistry in the evaluation of neovascularization in tumor xenografts. Biotech Histochem, 2008. 83(3-4): p. 179-89.
124.Werfel, T., et al., The diagnosis and graded therapy of atopic dermatitis. Dtsch Arztebl Int, 2014. 111(29-30): p. 509-20, i.
125.Eichenfield, L.F., Consensus guidelines in diagnosis and treatment of atopic dermatitis. Allergy, 2004. 59 Suppl 78: p. 86-92.
126.Hengge, U.R., et al., Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol, 2006. 54(1): p. 1-15; quiz 16-8.
127.Darsow, U., et al., Difficult to control atopic dermatitis. World Allergy Organ J, 2013. 6(1): p. 6.
128.Pariser, D., Topical corticosteroids and topical calcineurin inhibitors in the treatment of atopic dermatitis: focus on percutaneous absorption. Am J Ther, 2009. 16(3): p. 264-73.
129.Eichenfield, L.F., et al., Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol, 2014. 71(1): p. 116-32.
130.Breuer, K., T. Werfel, and A. Kapp, Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. Am J Clin Dermatol, 2005. 6(2): p. 65-77.
131.Baldo, A., et al., Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol, 2009. 2: p. 1-7.
132.Rustin, M.H., The safety of tacrolimus ointment for the treatment of atopic dermatitis: a review. Br J Dermatol, 2007. 157(5): p. 861-73.
133.Nghiem, P., G. Pearson, and R.G. Langley, Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol, 2002. 46(2): p. 228-41.
134.Fleischer, A.B., Jr., Treatment of atopic dermatitis: role of tacrolimus ointment as a topical noncorticosteroidal therapy. J Allergy Clin Immunol, 1999. 104(3 Pt 2): p. S126-30.
135.Kapp, A., B.R. Allen, and S. Reitamo, Atopic dermatitis management with tacrolimus ointment (Protopic). J Dermatolog Treat, 2003. 14(Suppl 1): p. 5-16.
136.Kang, S., et al., Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol, 2001. 44(1 Suppl): p. S58-64.
137.Lee, H.H., T. Zuberbier, and M. Worm, Treatment of atopic dermatitis with pimecrolimus - impact on quality of life. Ther Clin Risk Manag, 2007. 3(6): p. 1021-6.
138.Stuetz, A., et al., Discovery of topical calcineurin inhibitors and pharmacological profile of pimecrolimus. Int Arch Allergy Immunol, 2006. 141(3): p. 199-212.
139.Cury Martins, J., et al., Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev, 2015. 7: p. CD009864.
140.Siegfried, E.C., J.C. Jaworski, and A.A. Hebert, Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol, 2013. 14(3): p. 163-78.
141.Abramovits, W., M. Boguniewicz, and G. Adult Atopiclair Study, A multicenter, randomized, vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair) in the management of mild to moderate atopic dermatitis in adults. J Drugs Dermatol, 2006. 5(3): p. 236-44.
142.Kanno, S., et al., Inhibitory effect of naringin on lipopolysaccharide (LPS)-induced endotoxin shock in mice and nitric oxide production in RAW 264.7 macrophages. Life Sci, 2006. 78(7): p. 673-81.
143.Wang, Q.S., et al., Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-kappaB inactivation. PLoS One, 2012. 7(3): p. e34122.
144.Norrby, K., In vivo models of angiogenesis. J Cell Mol Med, 2006. 10(3): p. 588-612.
145.Staton, C.A., M.W. Reed, and N.J. Brown, A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol, 2009. 90(3): p. 195-221.
146.Rubinstein, A.L., Zebrafish: from disease modeling to drug discovery. Curr Opin Drug Discov Devel, 2003. 6(2): p. 218-23.
147.Lawson, N.D. and B.M. Weinstein, Arteries and veins: making a difference with zebrafish. Nat Rev Genet, 2002. 3(9): p. 674-82.
148.Jin, H., et al., Animal models of atopic dermatitis. J Invest Dermatol, 2009. 129(1): p. 31-40.
149.Tanaka, A., et al., Recent findings in mouse models for human atopic dermatitis. Exp Anim, 2012. 61(2): p. 77-84.
150.Avci, P., et al., Animal models of skin disease for drug discovery. Expert Opin Drug Discov, 2013. 8(3): p. 331-55.
151.Man, M.Q., et al., Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol, 2008. 128(1): p. 79-86.
152.Lee, K.S., Jeong, E.S.,Heo, S.H.,Seo, J.H.,Jeong, D.G.,Choi, Y.K., , A Novel Model for Human Atopic Dermatitis: Application of Repeated DNCB Patch in BALB/c Mice, in Comparison with NC/Nga Mice. 2010.
153.Saarnilehto, M., et al., Contact sensitizer 2,4-dinitrochlorobenzene is a highly potent human TRPA1 agonist. Allergy, 2014. 69(10): p. 1424-7.
154.Zhang, E.Y., A.Y. Chen, and B.T. Zhu, Mechanism of dinitrochlorobenzene-induced dermatitis in mice: role of specific antibodies in pathogenesis. PLoS One, 2009. 4(11): p. e7703.
155.Grabbe, S. and T. Schwarz, Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today, 1998. 19(1): p. 37-44.
156.Watanabe, H., et al., Contact hypersensitivity: the mechanism of immune responses and T cell balance. J Interferon Cytokine Res, 2002. 22(4): p. 407-12.
157.Belij, S., et al., Systemic immunomodulatory effects of topical dinitrochlorobenzene (DNCB) in rats. Activity of peripheral blood polymorphonuclear cells. Environ Toxicol Pharmacol, 2012. 33(2): p. 168-80.
158.Hu, G.P., et al., Statistical research on marine natural products based on data obtained between 1985 and 2008. Mar Drugs, 2011. 9(4): p. 514-25.
159.Rocha-Martin, J., et al., Emerging strategies and integrated systems microbiology technologies for biodiscovery of marine bioactive compounds. Mar Drugs, 2014. 12(6): p. 3516-59.
160.Martins, A., et al., Marketed marine natural products in the pharmaceutical and cosmeceutical industries: tips for success. Mar Drugs, 2014. 12(2): p. 1066-101.
161.Senthilkumar, K. and S.K. Kim, Marine invertebrate natural products for anti-inflammatory and chronic diseases. Evid Based Complement Alternat Med, 2013. 2013: p. 572859.
162.Villa, F.A. and L. Gerwick, Marine natural product drug discovery: Leads for treatment of inflammation, cancer, infections, and neurological disorders. Immunopharmacol Immunotoxicol, 2010. 32(2): p. 228-37.
163.Jin, L., et al., Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi. Mar Drugs, 2016. 14(4).
164.Rateb, M.E. and R. Ebel, Secondary metabolites of fungi from marine habitats. Nat Prod Rep, 2011. 28(2): p. 290-344.
165.Malve, H., Exploring the ocean for new drug developments: Marine pharmacology. J Pharm Bioallied Sci, 2016. 8(2): p. 83-91.
166.Thomas, N.V. and S.K. Kim, Beneficial effects of marine algal compounds in cosmeceuticals. Mar Drugs, 2013. 11(1): p. 146-64.
167.Dey, M., et al., In vitro and in vivo anti-inflammatory activity of a seed preparation containing phenethylisothiocyanate. J Pharmacol Exp Ther, 2006. 317(1): p. 326-33.
168.Choi, J.H., et al., Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-kappaB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1. Phytomedicine, 2014. 21(8-9): p. 1053-61.
169.Yang, G., et al., Effects of Catalpa ovata stem bark on atopic dermatitis-like skin lesions in NC/Nga mice. J Ethnopharmacol, 2013. 145(2): p. 416-23.
170.Dunster, J.L., The macrophage and its role in inflammation and tissue repair: mathematical and systems biology approaches. Wiley Interdiscip Rev Syst Biol Med, 2016. 8(1): p. 87-99.
171.Ghosh, C., et al., Anti-inflammatory activity of the ethanol extract of Dictamnus dasycarpus leaf in lipopolysaccharide-activated macrophages. BMC Complement Altern Med, 2014. 14: p. 330.
172.Senthil Kumar, K.J. and S.Y. Wang, Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-kappaB and MAPKs signaling pathways. Planta Med, 2009. 75(5): p. 494-500.
173.Choi, S.E., et al., Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice. Exp Dermatol, 2010. 19(8): p. e37-43.
174.Park, D.K., Y.G. Lee, and H.J. Park, Extract of Rhus verniciflua Bark Suppresses 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis. Evid Based Complement Alternat Med, 2013. 2013: p. 879696.
175.Shin, Y.W., et al., Effect of ginsenoside Rb1 and compound K in chronic oxazolone-induced mouse dermatitis. Int Immunopharmacol, 2005. 5(7-8): p. 1183-91.
176.Su-Jin Kim, J.-H.L., Chung Hwan Oh, Sa-Rang Oh and Ji-Wook Jung, Chungyangeum Attenuated the Allergic Inflammation in vivo and in vitro. Biomedical Science Letters, 2013.
177.Caivano, M. and P. Cohen, Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages. J Immunol, 2000. 164(6): p. 3018-25.
178.Jung, H.J., et al., Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown. J Ethnopharmacol, 2009. 126(2): p. 355-60.
179.Chesrown, S.E., et al., Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-gamma, TGF-beta, and IL-10 in murine macrophage cell lines and rat peritoneal macrophages. Biochem Biophys Res Commun, 1994. 200(1): p. 126-34.
180.Lim, E.J., et al., Anti-angiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol. J Pharm Pharmacol, 2007. 59(9): p. 1235-40.
181.Linde, A., et al., Innate immunity and inflammation--New frontiers in comparative cardiovascular pathology. Cardiovasc Res, 2007. 73(1): p. 26-36.
182.Kharraz, Y., et al., Macrophage plasticity and the role of inflammation in skeletal muscle repair. Mediators Inflamm, 2013. 2013: p. 491497.
183.Yang, H.L., et al., Induction of Nrf2-mediated genes by Antrodia salmonea inhibits ROS generation and inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages. Food Funct, 2015. 6(1): p. 230-41.
184.Willoughby, D.A., et al., Resolution of inflammation. Int J Immunopharmacol, 2000. 22(12): p. 1131-5.
185.Kikuchi, G., T. Yoshida, and M. Noguchi, Heme oxygenase and heme degradation. Biochem Biophys Res Commun, 2005. 338(1): p. 558-67.
186.Motterlini, R., C.J. Green, and R. Foresti, Regulation of heme oxygenase-1 by redox signals involving nitric oxide. Antioxid Redox Signal, 2002. 4(4): p. 615-24.
187.Sung, J., et al., Anti-inflammatory effect of methanol extract from Erigeron Canadensis L. may be involved with upregulation of heme oxygenase-1 expression and suppression of NFkappaB and MAPKs activation in macrophages. Nutr Res Pract, 2014. 8(4): p. 352-9.
188.Ishii, T., et al., Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem, 2000. 275(21): p. 16023-9.
189.Jin, C.H., et al., Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS/p38 MAPK/Nrf2 Pathway. Biomol Ther (Seoul), 2016. 24(5): p. 510-6.
190.Gozzelino, R., V. Jeney, and M.P. Soares, Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol, 2010. 50: p. 323-54.
191.Soares, M.P. and F.H. Bach, Heme oxygenase-1: from biology to therapeutic potential. Trends Mol Med, 2009. 15(2): p. 50-8.
192.Seixas, E., et al., Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci U S A, 2009. 106(37): p. 15837-42.
193.Cheng, H.W., et al., Polygonum viviparum L. inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through haem oxygenase-1 induction and activation of the Nrf2 pathway. J Sci Food Agric, 2013. 93(3): p. 491-7.
194.Tsai, P.S., et al., Heme oxygenase 1, nuclear factor E2-related factor 2, and nuclear factor kappaB are involved in hemin inhibition of type 2 cationic amino acid transporter expression and L-Arginine transport in stimulated macrophages. Anesthesiology, 2006. 105(6): p. 1201-10; discussion 5A.
195.Lee, M.Y., et al., Anti-inflammatory activity of Angelica dahurica ethanolic extract on RAW264.7 cells via upregulation of heme oxygenase-1. Food Chem Toxicol, 2011. 49(5): p. 1047-55.
196.Folkman, J., Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1995. 1(1): p. 27-31.
197.Hudson, N., et al., Angiogenesis in gastric ulcers: impaired in patients taking non-steroidal anti-inflammatory drugs. Gut, 1995. 37(2): p. 191-4.
198.Alam, C.A., M.P. Seed, and D.A. Willoughby, Angiostasis and vascular regression in chronic granulomatous inflammation induced by diclofenac in combination with hyaluronan in mice. J Pharm Pharmacol, 1995. 47(5): p. 407-11.
199.Colville-Nash, P.R., et al., The pharmacological modulation of angiogenesis in chronic granulomatous inflammation. J Pharmacol Exp Ther, 1995. 274(3): p. 1463-72.
200.Dermond, O. and C. Ruegg, Inhibition of tumor angiogenesis by non-steroidal anti-inflammatory drugs: emerging mechanisms and therapeutic perspectives. Drug Resist Updat, 2001. 4(5): p. 314-21.
201.Monnier, Y., J. Zaric, and C. Ruegg, Inhibition of angiogenesis by non-steroidal anti-inflammatory drugs: from the bench to the bedside and back. Curr Drug Targets Inflamm Allergy, 2005. 4(1): p. 31-8.
202.Jung, H.J., et al., Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin. Arch Pharm Res, 2010. 33(2): p. 309-16.
203.Alex, D., et al., Indirubin shows anti-angiogenic activity in an in vivo zebrafish model and an in vitro HUVEC model. J Ethnopharmacol, 2010. 131(2): p. 242-7.
204.Tang, J.Y., et al., Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. PLoS One, 2010. 5(7): p. e11822.
205.Gore, A.V., et al., Vascular development in the zebrafish. Cold Spring Harb Perspect Med, 2012. 2(5): p. a006684.
206.Sykes, B.G., et al., The Relationship between Estrogen and Nitric Oxide in the Prevention of Cardiac and Vascular Anomalies in the Developing Zebrafish (Danio Rerio). Brain Sci, 2016. 6(4).
207.Wen, Z.H., et al., A neuroprotective sulfone of marine origin and the in vivo anti-inflammatory activity of an analogue. Eur J Med Chem, 2010. 45(12): p. 5998-6004.
208.Lin, S.W., et al., Coral-derived compound WA-25 inhibits angiogenesis by attenuating the VEGF/VEGFR2 signaling pathway. Mar Drugs, 2015. 13(2): p. 861-78.
209.Lin, C., M. Wu, and J. Dong, Quercetin-4''-O-beta-D-glucopyranoside (QODG) inhibits angiogenesis by suppressing VEGFR2-mediated signaling in zebrafish and endothelial cells. PLoS One, 2012. 7(2): p. e31708.
210.Zhang, Z.R., et al., In vivo angiogenesis screening and mechanism of action of novel tanshinone derivatives produced by one-pot combinatorial modification of natural tanshinone mixture from Salvia miltiorrhiza. PLoS One, 2014. 9(7): p. e100416.
211.Newell, L., et al., Sensitization via healthy skin programs Th2 responses in individuals with atopic dermatitis. J Invest Dermatol, 2013. 133(10): p. 2372-80.
212.Hartman, A., P.J. Hoedemaeker, and J.P. Nater, Histological aspects of DNCB sensitization and challenge tests. Br J Dermatol, 1976. 94(4): p. 407-16.
213.Alshammari Fanar Hamad, J.-H.H., Irfan Ahmad Rather, Mouse model of DNCB-induced atopic dermatitis. Bangladesh Journal of Pharmacology, 2017. 12.
214.Matsuoka, H., et al., A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae. Allergy, 2003. 58(2): p. 139-45.
215.Han, M.H., et al., Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice. Int Immunopharmacol, 2007. 7(13): p. 1651-8.
216.Chan, C.C., et al., Effect of dehydroepiandrosterone on atopic dermatitis-like skin lesions induced by 1-chloro-2,4-dinitrobenzene in mouse. J Dermatol Sci, 2013. 72(2): p. 149-57.
217.Akdis, C.A., et al., Immune regulation in atopic dermatitis. Curr Opin Immunol, 2000. 12(6): p. 641-6.
218.Kim, S.R., et al., Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice. Mediators Inflamm, 2014. 2014: p. 319438.
219.Boguniewicz, M., P. Schmid-Grendelmeier, and D.Y. Leung, Atopic dermatitis. J Allergy Clin Immunol, 2006. 118(1): p. 40-3.
220.Kim, W.Y., et al., A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model. Molecules, 2015. 21(1): p. E35.
221.Li, Y.Z., et al., Anti-inflammatory effect of qingpeng ointment in atopic dermatitis-like murine model. Evid Based Complement Alternat Med, 2013. 2013: p. 907016.
222.Dang, L., et al., Role of the complement anaphylatoxin C5a-receptor pathway in atopic dermatitis in mice. Mol Med Rep, 2015. 11(6): p. 4183-9.
223.Jaffe, R., Atopic dermatitis. Prim Care, 2000. 27(2): p. 503-13.
224.Mansouri, Y. and E. Guttman-Yassky, Immune Pathways in Atopic Dermatitis, and Definition of Biomarkers through Broad and Targeted Therapeutics. J Clin Med, 2015. 4(5): p. 858-73.
225.Werfel, T., et al., Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis. J Invest Dermatol, 1996. 107(6): p. 871-6.
226.Lee, S.J., et al., Oral administration of Astragalus membranaceus inhibits the development of DNFB-induced dermatitis in NC/Nga mice. Biol Pharm Bull, 2007. 30(8): p. 1468-71.
227.Suzuki, Y., et al., Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science, 1988. 240(4851): p. 516-8.
228.Valledor, A.F., et al., Macrophage proinflammatory activation and deactivation: a question of balance. Adv Immunol, 2010. 108: p. 1-20.
229.Sur, B., et al., Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice. BMC Complement Altern Med, 2016. 16: p. 38.
230.Hwang, J.S., et al., Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum. BMC Complement Altern Med, 2013. 13: p. 312.
231.Kim, H.R., et al., Hyperoxygenation attenuated a murine model of atopic dermatitis through raising skin level of ROS. PLoS One, 2014. 9(10): p. e109297.
232.McCormick, T.S., S.R. Stevens, and K. Kang, Macrophages and cutaneous inflammation. Nat Biotechnol, 2000. 18(1): p. 25-6.
233.Gordon, S., Alternative activation of macrophages. Nat Rev Immunol, 2003. 3(1): p. 23-35.
234.Stuehr, D.J., Mammalian nitric oxide synthases. Biochim Biophys Acta, 1999. 1411(2-3): p. 217-30.
235.Cassini-Vieira, P., et al., iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants. Mediators Inflamm, 2015. 2015: p. 138461.
236.Guzik, T.J., et al., Nitric oxide metabolite levels in children and adult patients with atopic eczema/dermatitis syndrome. Allergy, 2002. 57(9): p. 856.
237.Williams, C.S., M. Mann, and R.N. DuBois, The role of cyclooxygenases in inflammation, cancer, and development. Oncogene, 1999. 18(55): p. 7908-16.
238.Aoki, T. and S. Narumiya, Prostaglandins and chronic inflammation. Trends Pharmacol Sci, 2012. 33(6): p. 304-11.
239.Wei, W.C., et al., Topical application of marine briarane-type diterpenes effectively inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and dermatitis in murine skin. J Biomed Sci, 2011. 18: p. 94.
240.Cha, H.Y., et al., Hataedock Treatment Has Preventive Therapeutic Effects in Atopic Dermatitis-Induced NC/Nga Mice under High-Fat Diet Conditions. Evid Based Complement Alternat Med, 2016. 2016: p. 1739760.
241.NAITO, T.Y.Y., What Is Oxidative Stress? JMAJ, 2002. 124.
242.Trouba, K.J., et al., Oxidative stress and its role in skin disease. Antioxid Redox Signal, 2002. 4(4): p. 665-73.
243.Fuchs, J., et al., Redox-modulated pathways in inflammatory skin diseases. Free Radic Biol Med, 2001. 30(4): p. 337-53.
244.Ji, H. and X.K. Li, Oxidative Stress in Atopic Dermatitis. Oxid Med Cell Longev, 2016. 2016: p. 2721469.
245.Xin, G., et al., Effect of oxidative stress on heme oxygenase-1 expression in patients with gestational diabetes mellitus. Exp Ther Med, 2014. 7(2): p. 478-482.
246.Wagener, F.A., C.E. Carels, and D.M. Lundvig, Targeting the redox balance in inflammatory skin conditions. Int J Mol Sci, 2013. 14(5): p. 9126-67.
247.Hybertson, B.M., et al., Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med, 2011. 32(4-6): p. 234-46.
248.Fang, J., T. Seki, and H. Maeda, Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Adv Drug Deliv Rev, 2009. 61(4): p. 290-302.
249.Motterlini, R., et al., Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med, 2000. 28(8): p. 1303-12.
250.Ryter, S.W., J. Alam, and A.M. Choi, Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev, 2006. 86(2): p. 583-650.
251.Chora, A.A., et al., Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J Clin Invest, 2007. 117(2): p. 438-47.
252.Pae, H.O. and H.T. Chung, Heme oxygenase-1: its therapeutic roles in inflammatory diseases. Immune Netw, 2009. 9(1): p. 12-9.
253.Lin, H.Y., S.C. Shen, and Y.C. Chen, Anti-inflammatory effect of heme oxygenase 1: glycosylation and nitric oxide inhibition in macrophages. J Cell Physiol, 2005. 202(2): p. 579-90.
254.Zamora, R., Y. Vodovotz, and T.R. Billiar, Inducible nitric oxide synthase and inflammatory diseases. Mol Med, 2000. 6(5): p. 347-73.
255.Carmeliet, P. and R.K. Jain, Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011. 473(7347): p. 298-307.
256.Hussain, Z., et al., Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles. Int J Nanomedicine, 2014. 9: p. 5143-56.
257.Koczy-Baron, E., J. Jochem, and A. Kasperska-Zajac, Increased plasma concentration of vascular endothelial growth factor in patients with atopic dermatitis and its relation to disease severity and platelet activation. Inflamm Res, 2012. 61(12): p. 1405-9.
258.Pusztaszeri, M.P., W. Seelentag, and F.T. Bosman, Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem, 2006. 54(4): p. 385-95.
259.DeLisser, H.M., et al., Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol, 1997. 151(3): p. 671-7.
260.De Young, B.R., et al., CD31 immunoreactivity in carcinomas and mesotheliomas. Am J Clin Pathol, 1998. 110(3): p. 374-7.
261.Zanetta, L., et al., Expression of Von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis. Int J Cancer, 2000. 85(2): p. 281-8.
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