臺灣博碩士論文加值系統

豆固醇 (stigmasterol) 為一不飽和植物固醇，目前已被研究出多種生物活性，如：抗發炎反應、抗癌、抗微生物及抗骨關節炎；根據文獻stigmasterol對於發炎體活性的影響尚未釐清，本實驗以巨噬細胞J774A.1與RAW264.7細胞株作為細胞模式，探討其對於發炎體活性之影響。首先藉由LPS與ATP誘發巨噬細胞NLRP3發炎體活化，利用酵素連結免疫吸附分析法 (ELISA) 與西方墨點法 (Western blot) 觀察發炎相關蛋白質IL-1β之分泌與caspase-1活性，並且利用西方墨點法評估NLRP3 發炎體活性。結果證實，stigmasterol能藉由抑制LPS刺激之NLRP3表現，並降低LPS/ATP誘導之IL-1β分泌量與caspase-1活性，並且stigmasterol也能降低由LPS誘導之NLRP3與IL-1β前驅物之蛋白表現量。在抑制NLRP3發炎體活性相關機制方面，stigmasterol已被證實能降低由ATP所誘導出之磷酸化ERK1/2，但JNK1/2、PKC-α與 PKC-δ則沒有明顯效果。另一方面，stigmasterol能有效抑制多種NLRP3誘導劑 (ATP、SiO2、CPPD與Alum) 誘發之IL-1β分泌；並且也能減少MDP與FLA-ST活化之NLRP1與 NLRC4發炎體分泌的IL-1β。由上述結果證實了stigmasterol能抑制經由LPS與多種NLRP3誘導劑活化之NLRP3發炎體活性，以及抑制NLRP1與 NLRC4發炎體活性。

Stigmasterol is an unsaturated plant sterol showing anti-inflammation, anti-cancer, anti-microbial, and anti-osteoarthritic; According to the previous reports, the effect of stigmasterol on inflammasome activation is unclear. To explor stigmasterol effect of inflammasome, using macrophage J774A.1 cell line, was treated by stigmasterol. At first, effect of stigmasterol on NLRP3 inflammasome activation in LPS- and ATP-activated macrophages was monitored by detecting IL-1β secretion and caspase-1 activation using ELISA and western blot, respectively. LPS- and ATP-mediated signaling associated with NLRP3 inflammasome activation were measured by western blot. Stigmasterol reduced IL-1β secretion and caspase-1 activation by inhibiting both LPS-activated and activation signal of NLRP3 inflammasome in LPS- and ATP-activated macrophages. The stigmasterol also reduced LPS-induced protein expression levels of NLRP3 and IL-1β precursor. The underlying mechanisms for the anti-NLRP3 inflammasome activity were demonstrated as reducing ATP-induced phosphorylation of ERK1/2, but not JNK1/2, PKC-α, and PKC-δ. On the other hand, stigmasterol can effectively inhibit induced inflammatory cytokines by variety of inducers (ATP、SiO2、CPPD and Alum). Stigmasterol also inhibited the activation by NLRP1and NLRC4 inducer (MDP and FLA-ST). These results demonstrate that stigmasterol inhibited NLRP3 inflammasome activation through reducing not only the priming signal, but also the activation signal, of NLRP3 inflammasome in LPS- and variety inducers -activated macrophages ; stigmasterol also reduced inflammasome activation by inducer of NLRP1 and NLRC4.

目錄
中文摘要 I
英文摘要 II
致謝 III
目錄 IV
第一章、緒論 1
第一節、 植物固醇 2
第一項、 植物固醇之特性 2
第二項、 植物固醇之分類 3
第三項、 植物固醇之結構 4
第二節、 豆固醇 (stigmasterol) 6
第一項、 stigmasterol特性 6
第三節、 發炎反應 7
第一項、 發炎反應誘導巨噬細胞活化 7
第二項、 脂多醣 (Lipopolysaccharide, LPS) 誘導發炎反應 10
第四節、 訊息傳遞路徑 13
第一項、 模式識別受體 (Toll-Like Receptor 4, TLR4) 13
第二項、 NLRP3發炎體 (inflammasome) 14
第三項、 有絲分裂活化蛋白質激酶 (Mitogen-activated protein kinase, MAPK) 訊息傳遞路徑 15
第五節、 發炎調控因子 17
第一項、 一氧化氮 (Nitric oxide, NO) 17
第二項、 介白素 (Interleukins) 18
第六節、 研究方向與動機 19
第二章、材料與方法 20
第一節、 實驗研究材料 21
第一項、 實驗細胞 21
第二項、 藥品及化學試劑 21
第三項、 分析試劑組 23
第四項、 抗體 23
第五項、 分析軟體 24
第六項、 儀器設備 25
第七項、 實驗用耗材 26
第二節、 研究方法 27
第一項、 細胞解凍 27
第二項、細胞繼代培養 28
第三項、 細胞數目測定 29
第四項、 細胞保存 31
第五項、 細胞存活率偵測分析 31
第六項、 一氧化氮之定量與分析 (Nitrite assay) 32
第七項、 蛋白質定量法 (Bradford dye-binding method) 34
第八項、 十二烷基磺酸鈉-聚丙烯醯胺膠電泳 (Sodium dodecyl sulfate-polycarylamide gelelectrophoresis, SDS-PAGE) 36
第九項、 西方墨點法 (Western blot) 37
第十項、 酵素連結免疫吸附法 (Enzyme-linked Immunosorbent Assay, ELISA) 39
第十一項、細胞內活性氧化物含量分析 41
第十二項、統計分析 41
第三章、研究結果 42
第一節、stigmasterol 對於巨噬細胞存活率之影響 43
第二節、stigmasterol抑制由LPS所誘發之NO表現 44
第三節、stigmasterol對IL-1β與TNF-α之影響 45
第四節、stigmasterol抑制由LPS刺激之ROS表現 49
第四節、stigmasterol抑制由ATP刺激之ROS表現 50
第五節、stigmasterol抑制NLRP3發炎體之活化 51
第六節、stigmasterol於ATP刺激下抑制p-ERK 53
第七節、stigmasterol於Nigericin刺激下IL-1β之影響 54
第八節、stigmasterol於Nigericin刺激下Caspase-1之影響 55
第九節、stigmasterol於SiO2刺激下IL-1β之影響 56
第十節、stigmasterol於CPPD刺激下IL-1β之影響 57
第十一節、stigmasterol於Alum刺激下IL-1β之影響 58
第十二節、stigmasterol於MDP刺激下IL-1β與TNF-α之影響 59
第十三節、stigmasterol於MDP刺激下Caspase-1之影響 61
第十四節、stigmasterol於FLA-ST刺激下IL-1β與TNF-α之影響 62
第四章、討論 64
第一節、stigmasterol之生理活性 65
第一節、stigmasterol於巨噬細胞存活率測試 66
第三節、stigmasterol抗發炎活性分析 67
第四節、stigmasterol於NLRP3 inflammasome影響 69
第五節、stigmasterol於NLRP1與NLRC4 inflammasome影響 70
第五章、結論 72
第六章、圖表說明 74
參考文獻 77

Ahmed, Y., M. H. Sohrab, S. M. Al-Reza, F. S. Tareq, C. M. Hasan, and M. A. Sattar. "Antimicrobial and Cytotoxic Constituents from Leaves of Sapium Baccatum." Food Chem Toxicol 48, no. 2 (2010): 549-52.
Akira, S., K. Takeda, and T. Kaisho. "Toll-Like Receptors: Critical Proteins Linking Innate and Acquired Immunity." Nat Immunol 2, no. 8 (2001): 675-80.
Alemany, L., J. M. Laparra, R. Barbera, and A. Alegria. "Evaluation of the Cytotoxic Effect of 7keto-Stigmasterol and 7keto-Cholesterol in Human Intestinal (Caco-2) Cells." Food Chem Toxicol 50, no. 9 (2012): 3106-13.
Auron, P. E., A. C. Webb, L. J. Rosenwasser, S. F. Mucci, A. Rich, S. M. Wolff, and C. A. Dinarello. "Nucleotide Sequence of Human Monocyte Interleukin 1 Precursor Cdna." Proc Natl Acad Sci U S A 81, no. 24 (1984): 7907-11.
Bak, M. J., S. G. Hong, J. W. Lee, and W. S. Jeong. "Red Ginseng Marc Oil Inhibits Inos and Cox-2 Via Nfkappab and P38 Pathways in Lps-Stimulated Raw 264.7 Macrophages." Molecules 17, no. 12 (2012): 13769-86.
Batta, A. K., G. Xu, A. Honda, T. Miyazaki, and G. Salen. "Stigmasterol Reduces Plasma Cholesterol Levels and Inhibits Hepatic Synthesis and Intestinal Absorption in the Rat." Metabolism 55, no. 3 (2006): 292-9.
Baudouin, C., P. Hamard, H. Liang, C. Creuzot-Garcher, L. Bensoussan, and F. Brignole. "Conjunctival Epithelial Cell Expression of Interleukins and Inflammatory Markers in Glaucoma Patients Treated over the Long Term." Ophthalmology 111, no. 12 (2004): 2186-92.
Bouic, P. J., and J. H. Lamprecht. "Plant Sterols and Sterolins: A Review of Their Immune-Modulating Properties." Altern Med Rev 4, no. 3 (1999): 170-7.
Brimson, J. M., S. J. Brimson, C. A. Brimson, V. Rakkhitawatthana, and T. Tencomnao. "Rhinacanthus Nasutus Extracts Prevent Glutamate and Amyloid-Beta Neurotoxicity in Ht-22 Mouse Hippocampal Cells: Possible Active Compounds Include Lupeol, Stigmasterol and Beta-Sitosterol." Int J Mol Sci 13, no. 4 (2012): 5074-97.
Cai, S., S. Batra, N. Wakamatsu, P. Pacher, and S. Jeyaseelan. "Nlrc4 Inflammasome-Mediated Production of Il-1beta Modulates Mucosal Immunity in the Lung against Gram-Negative Bacterial Infection." J Immunol 188, no. 11 (2012): 5623-35.
Caroff, M., D. Karibian, J. M. Cavaillon, and N. Haeffner-Cavaillon. "Structural and Functional Analyses of Bacterial Lipopolysaccharides." Microbes Infect 4, no. 9 (2002): 915-26.

Carter, B. A., O. A. Taylor, D. R. Prendergast, T. L. Zimmerman, R. Von Furstenberg, D. D. Moore, and S. J. Karpen. "Stigmasterol, a Soy Lipid-Derived Phytosterol, Is an Antagonist of the Bile Acid Nuclear Receptor Fxr." Pediatr Res 62, no. 3 (2007): 301-6.
Chen, C. C., S. H. Tsai, C. C. Lu, S. T. Hu, T. S. Wu, T. T. Huang, N. Said-Sadier, D. M. Ojcius, and H. C. Lai. "Activation of an Nlrp3 Inflammasome Restricts Mycobacterium Kansasii Infection." PLoS One 7, no. 4 (2012): e36292.
Chen, W. P., C. Yu, P. F. Hu, J. P. Bao, J. L. Tang, and L. D. Wu. "Stigmasterol Blocks Cartilage Degradation in Rabbit Model of Osteoarthritis." Acta Biochim Pol 59, no. 4 (2012): 537-41.
Chen, Y. C., S. C. Shen, L. G. Chen, T. J. Lee, and L. L. Yang. "Wogonin, Baicalin, and Baicalein Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Gene Expressions Induced by Nitric Oxide Synthase Inhibitors and Lipopolysaccharide." Biochem Pharmacol 61, no. 11 (2001): 1417-27.
Chumkaew, P., S. Kato, and K. Chantrapromma. "New Cytotoxic Steroids from the Fruits of Syzygium Siamense." J Asian Nat Prod Res 12, no. 5 (2010): 424-8.
Conforti-Andreoni, C., P. Ricciardi-Castagnoli, and A. Mortellaro. "The Inflammasomes in Health and Disease: From Genetics to Molecular Mechanisms of Autoinflammation and Beyond." Cell Mol Immunol 8, no. 2 (2011): 135-45.
de Roos, N. M., E. G. Schouten, and M. B. Katan. "Trans Fatty Acids, Hdl-Cholesterol, and Cardiovascular Disease. Effects of Dietary Changes on Vascular Reactivity." Eur J Med Res 8, no. 8 (2003): 355-7.
Delbridge, L. M., and M. X. O'Riordan. "Innate Recognition of Intracellular Bacteria." Curr Opin Immunol 19, no. 1 (2007): 10-6.
Dong, W., Y. Liu, J. Peng, L. Chen, T. Zou, H. Xiao, Z. Liu, et al. "The Irak-1-Bcl10-Malt1-Traf6-Tak1 Cascade Mediates Signaling to Nf-Kappab from Toll-Like Receptor 4." J Biol Chem 281, no. 36 (2006): 26029-40.
Erridge, C., J. Stewart, E. Bennett-Guerrero, T. J. McIntosh, and I. R. Poxton. "The Biological Activity of a Liposomal Complete Core Lipopolysaccharide Vaccine." J Endotoxin Res 8, no. 1 (2002): 39-46.
Faustin, B., L. Lartigue, J. M. Bruey, F. Luciano, E. Sergienko, B. Bailly-Maitre, N. Volkmann, et al. "Reconstituted Nalp1 Inflammasome Reveals Two-Step Mechanism of Caspase-1 Activation." Mol Cell 25, no. 5 (2007): 713-24.
Fettelschoss, A., M. Kistowska, S. LeibundGut-Landmann, H. D. Beer, P. Johansen, G. Senti, E. Contassot, et al. "Inflammasome Activation and Il-1beta Target Il-1alpha for Secretion as Opposed to Surface Expression." Proc Natl Acad Sci U S A 108, no. 44 (2011): 18055-60.

Fink, S. L., and B. T. Cookson. "Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells." Infect Immun 73, no. 4 (2005): 1907-16.
Fitzgerald, K. A. "Nlr-Containing Inflammasomes: Central Mediators of Host Defense and Inflammation." Eur J Immunol 40, no. 3 (2010): 595-8.
Franchi, L., N. Kamada, Y. Nakamura, A. Burberry, P. Kuffa, S. Suzuki, M. H. Shaw, Y. G. Kim, and G. Nunez. "Nlrc4-Driven Production of Il-1beta Discriminates between Pathogenic and Commensal Bacteria and Promotes Host Intestinal Defense." Nat Immunol 13, no. 5 (2012): 449-56.
Furchgott, R. F., and J. V. Zawadzki. "The Obligatory Role of Endothelial Cells in the Relaxation of Arterial Smooth Muscle by Acetylcholine." Nature 288, no. 5789 (1980): 373-6.
Gabay, O., C. Sanchez, C. Salvat, F. Chevy, M. Breton, G. Nourissat, C. Wolf, C. Jacques, and F. Berenbaum. "Stigmasterol: A Phytosterol with Potential Anti-Osteoarthritic Properties." Osteoarthritis Cartilage 18, no. 1 (2010): 106-16.
Gery, I., R. K. Gershon, and B. H. Waksman. "Potentiation of Cultured Mouse Thymocyte Responses by Factors Released by Peripheral Leucocytes." J Immunol 107, no. 6 (1971): 1778-80.
Glauser, M. P., D. Heumann, J. D. Baumgartner, and J. Cohen. "Pathogenesis and Potential Strategies for Prevention and Treatment of Septic Shock: An Update." Clin Infect Dis 18 Suppl 2 (1994): S205-16.
Gong, Y. N., and F. Shao. "Sensing Bacterial Infections by Naip Receptors in Nlrc4 Inflammasome Activation." Protein Cell 3, no. 2 (2012): 98-105.
Gonzalez-Gallego, J., S. Sanchez-Campos, and M. J. Tunon. "Anti-Inflammatory Properties of Dietary Flavonoids." Nutr Hosp 22, no. 3 (2007): 287-93.
Goyert, S. M., E. Ferrero, W. J. Rettig, A. K. Yenamandra, F. Obata, and M. M. Le Beau. "The Cd14 Monocyte Differentiation Antigen Maps to a Region Encoding Growth Factors and Receptors." Science 239, no. 4839 (1988): 497-500.
Gradisar, H., M. M. Keber, P. Pristovsek, and R. Jerala. "Md-2 as the Target of Curcumin in the Inhibition of Response to Lps." J Leukoc Biol 82, no. 4 (2007): 968-74.
Griebel, T., and J. Zeier. "A Role for Beta-Sitosterol to Stigmasterol Conversion in Plant-Pathogen Interactions." Plant J 63, no. 2 (2010): 254-68.
Guha, M., and N. Mackman. "Lps Induction of Gene Expression in Human Monocytes." Cell Signal 13, no. 2 (2001): 85-94.
Hayashi, F., K. D. Smith, A. Ozinsky, T. R. Hawn, E. C. Yi, D. R. Goodlett, J. K. Eng, et al. "The Innate Immune Response to Bacterial Flagellin Is Mediated by Toll-Like Receptor 5." Nature 410, no. 6832 (2001): 1099-103.

Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, et al. "A Toll-Like Receptor Recognizes Bacterial DNA." Nature 408, no. 6813 (2000): 740-5.
Hoshi, M., E. Nishida, and H. Sakai. "Activation of a Ca2+-Inhibitable Protein Kinase That Phosphorylates Microtubule-Associated Protein 2 in Vitro by Growth Factors, Phorbol Esters, and Serum in Quiescent Cultured Human Fibroblasts." J Biol Chem 263, no. 11 (1988): 5396-401.
Inohara, N., and G. Nunez. "Nods: Intracellular Proteins Involved in Inflammation and Apoptosis." Nat Rev Immunol 3, no. 5 (2003): 371-82.
Jin, C., and R. A. Flavell. "Molecular Mechanism of Nlrp3 Inflammasome Activation." J Clin Immunol 30, no. 5 (2010): 628-31.
Kagan, J. C., T. Su, T. Horng, A. Chow, S. Akira, and R. Medzhitov. "Tram Couples Endocytosis of Toll-Like Receptor 4 to the Induction of Interferon-Beta." Nat Immunol 9, no. 4 (2008): 361-8.
Kato, Y., V. V. Kravchenko, R. I. Tapping, J. Han, R. J. Ulevitch, and J. D. Lee. "Bmk1/Erk5 Regulates Serum-Induced Early Gene Expression through Transcription Factor Mef2c." EMBO J 16, no. 23 (1997): 7054-66.
Kawai, T., and S. Akira. "The Role of Pattern-Recognition Receptors in Innate Immunity: Update on Toll-Like Receptors." Nat Immunol 11, no. 5 (2010): 373-84.
Kerckhoffs, D. A., F. Brouns, G. Hornstra, and R. P. Mensink. "Effects on the Human Serum Lipoprotein Profile of Beta-Glucan, Soy Protein and Isoflavones, Plant Sterols and Stanols, Garlic and Tocotrienols." J Nutr 132, no. 9 (2002): 2494-505.
Khare, S., N. Luc, A. Dorfleutner, and C. Stehlik. "Inflammasomes and Their Activation." Crit Rev Immunol 30, no. 5 (2010): 463-87.
Kiem, P. V., N. T. Thuy, T. Anh Hle, N. X. Nhiem, C. V. Minh, P. H. Yen, N. K. Ban, et al. "Chemical Constituents of the Rhizomes of Hedychium Coronarium and Their Inhibitory Effect on the Pro-Inflammatory Cytokines Production Lps-Stimulated in Bone Marrow-Derived Dendritic Cells." Bioorg Med Chem Lett 21, no. 24 (2011): 7460-5.
Kronheim, S. R., C. J. March, S. K. Erb, P. J. Conlon, D. Y. Mochizuki, and T. P. Hopp. "Human Interleukin 1. Purification to Homogeneity." J Exp Med 161, no. 3 (1985): 490-502.
Latz, E. "The Inflammasomes: Mechanisms of Activation and Function." Curr Opin Immunol 22, no. 1 (2010): 28-33.
Levinsohn, J. L., Z. L. Newman, K. A. Hellmich, R. Fattah, M. A. Getz, S. Liu, I. Sastalla, S. H. Leppla, and M. Moayeri. "Anthrax Lethal Factor Cleavage of Nlrp1 Is Required for Activation of the Inflammasome." PLoS Pathog 8, no. 3 (2012): e1002638.
Lin, L. C., C. C. Shen, Y. C. Shen, and T. H. Tsai. "Anti-Inflammatory Neolignans from Piper Kadsura." J Nat Prod 69, no. 5 (2006): 842-4.
March, C. J., B. Mosley, A. Larsen, D. P. Cerretti, G. Braedt, V. Price, S. Gillis, et al. "Cloning, Sequence and Expression of Two Distinct Human Interleukin-1 Complementary Dnas." Nature 315, no. 6021 (1985): 641-7.
Medzhitov, R. "Inflammation 2010: New Adventures of an Old Flame." Cell 140, no. 6 (2010): 771-6.
Medzhitov, R., and C. A. Janeway, Jr. "Innate Immunity: The Virtues of a Nonclonal System of Recognition." Cell 91, no. 3 (1997): 295-8.
Meylan, E., J. Tschopp, and M. Karin. "Intracellular Pattern Recognition Receptors in the Host Response." Nature 442, no. 7098 (2006): 39-44.
Mitka, M. "1998 Nobel Prize Winners Are Announced: Three Discoverers of Nitric Oxide Activity." JAMA 280, no. 19 (1998): 1648.
Mizel, S. B., A. N. Honko, M. A. Moors, P. S. Smith, and A. P. West. "Induction of Macrophage Nitric Oxide Production by Gram-Negative Flagellin Involves Signaling Via Heteromeric Toll-Like Receptor 5/Toll-Like Receptor 4 Complexes." J Immunol 170, no. 12 (2003): 6217-23.
Moreau, R. A., B. D. Whitaker, and K. B. Hicks. "Phytosterols, Phytostanols, and Their Conjugates in Foods: Structural Diversity, Quantitative Analysis, and Health-Promoting Uses." Prog Lipid Res 41, no. 6 (2002): 457-500.
Nair, P. P., N. Turjman, G. Kessie, B. Calkins, G. T. Goodman, H. Davidovitz, and G. Nimmagadda. "Diet, Nutrition Intake, and Metabolism in Populations at High and Low Risk for Colon Cancer. Dietary Cholesterol, Beta-Sitosterol, and Stigmasterol." Am J Clin Nutr 40, no. 4 Suppl (1984): 927-30.
Netea, M. G., A. Simon, F. van de Veerdonk, B. J. Kullberg, J. W. Van der Meer, and L. A. Joosten. "Il-1beta Processing in Host Defense: Beyond the Inflammasomes." PLoS Pathog 6, no. 2 (2010): e1000661.
Nhiem, N. X., P. V. Kiem, C. V. Minh, B. H. Tai, T. H. Quang, K. S. Soung, J. E. Koo, Y. S. Koh, and Y. H. Kim. "Anti-Inflammatory Activity on Lps-Stimulated Dendritic Cells of Lupanetype Triterpenoids from the Leaves of Acanthopanax Koreanum." Arch Pharm Res 34, no. 10 (2011): 1593-8.
Nishimoto, S., and E. Nishida. "Mapk Signalling: Erk5 Versus Erk1/2." EMBO Rep 7, no. 8 (2006): 782-6.
Nordberg, J., and E. S. Arner. "Reactive Oxygen Species, Antioxidants, and the Mammalian Thioredoxin System." Free Radic Biol Med 31, no. 11 (2001): 1287-312.
O'Callaghan, Y. C., D. A. Foley, N. M. O'Connell, F. O. McCarthy, A. R. Maguire, and N. M. O'Brien. "Cytotoxic and Apoptotic Effects of the Oxidized Derivatives of Stigmasterol in the U937 Human Monocytic Cell Line." J Agric Food Chem 58, no. 19 (2010): 10793-8.

Panda, S., M. Jafri, A. Kar, and B. K. Meheta. "Thyroid Inhibitory, Antiperoxidative and Hypoglycemic Effects of Stigmasterol Isolated from Butea Monosperma." Fitoterapia 80, no. 2 (2009): 123-6.
Pandith, H., X. Zhang, S. Thongpraditchote, Y. Wongkrajang, W. Gritsanapan, and S. J. Baek. "Effect of Siam Weed Extract and Its Bioactive Component Scutellarein Tetramethyl Ether on Anti-Inflammatory Activity through Nf-Kappab Pathway." J Ethnopharmacol 147, no. 2 (2013): 434-41.
Park, Y., and T. P. Carr. "Unsaturated Fatty Acids and Phytosterols Regulate Cholesterol Transporter Genes in Caco-2 and Hepg2 Cell Lines." Nutr Res 33, no. 2 (2013): 154-61.
Pelegrin, P., and A. Surprenant. "Pannexin-1 Couples to Maitotoxin- and Nigericin-Induced Interleukin-1beta Release through a Dye Uptake-Independent Pathway." J Biol Chem 282, no. 4 (2007): 2386-94.
Pollak, O. J. "Reduction of Blood Cholesterol in Man." Circulation 7, no. 5 (1953): 702-6.
Qu, Y., L. Ramachandra, S. Mohr, L. Franchi, C. V. Harding, G. Nunez, and G. R. Dubyak. "P2x7 Receptor-Stimulated Secretion of Mhc Class Ii-Containing Exosomes Requires the Asc/Nlrp3 Inflammasome but Is Independent of Caspase-1." J Immunol 182, no. 8 (2009): 5052-62.
Radomski, M. W., R. M. Palmer, and S. Moncada. "Characterization of the L-Arginine:Nitric Oxide Pathway in Human Platelets." Br J Pharmacol 101, no. 2 (1990): 325-8.
Rietschel, E. T., and H. Brade. "Bacterial Endotoxins." Sci Am 267, no. 2 (1992): 54-61.
Rudzinska, M., J. Korczak, A. Gramza, E. Wasowicz, and P. C. Dutta. "Inhibition of Stigmasterol Oxidation by Antioxidants in Purified Sunflower Oil." J AOAC Int 87, no. 2 (2004): 499-504.
Sabeva, N. S., C. M. McPhaul, X. Li, T. J. Cory, D. J. Feola, and G. A. Graf. "Phytosterols Differentially Influence Abc Transporter Expression, Cholesterol Efflux and Inflammatory Cytokine Secretion in Macrophage Foam Cells." J Nutr Biochem 22, no. 8 (2011): 777-83.
Schaller, H. "The Role of Sterols in Plant Growth and Development." Prog Lipid Res 42, no. 3 (2003): 163-75.
Schroder, K., and J. Tschopp. "The Inflammasomes." Cell 140, no. 6 (Mar 19 2010): 821-32.
Shaw, P. J., M. F. McDermott, and T. D. Kanneganti. "Inflammasomes and Autoimmunity." Trends Mol Med 17, no. 2 (2011): 57-64.
Sun, L., L. Deng, C. K. Ea, Z. P. Xia, and Z. J. Chen. "The Traf6 Ubiquitin Ligase and Tak1 Kinase Mediate Ikk Activation by Bcl10 and Malt1 in T Lymphocytes." Mol Cell 14, no. 3 (2004): 289-301.


Tao, R., C. Z. Wang, and Z. W. Kong. "Antibacterial/Antifungal Activity and Synergistic Interactions between Polyprenols and Other Lipids Isolated from Ginkgo Biloba L. Leaves." Molecules 18, no. 2 (2013): 2166-82.
Teh, S. S., G. Cheng Lian Ee, S. H. Mah, Y. M. Lim, and M. Rahmani. "Mesua Beccariana (Clusiaceae), a Source of Potential Anti-Cancer Lead Compounds in Drug Discovery." Molecules 17, no. 9 (2012): 10791-800.
Thiers, H. "[the Value of Stigmasterol (R. Wulzen's Antistiffness Factor Essential for Guinea Pigs) in the Therapy of Rheumatic Diseases]." Rev Rhum Mal Osteoartic 20, no. 8-9 (1953): 636-43.
Tschopp, J., and K. Schroder. "Nlrp3 Inflammasome Activation: The Convergence of Multiple Signalling Pathways on Ros Production?". Nat Rev Immunol 10, no. 3 (2010): 210-5.
Usuki, S., T. Ariga, S. Dasgupta, T. Kasama, K. Morikawa, S. Nonaka, Y. Okuhara, M. Kise, and R. K. Yu. "Structural Analysis of Novel Bioactive Acylated Steryl Glucosides in Pre-Germinated Brown Rice Bran." J Lipid Res 49, no. 10 (2008): 2188-96.
van de Veerdonk, F. L., M. G. Netea, C. A. Dinarello, and L. A. Joosten. "Inflammasome Activation and Il-1beta and Il-18 Processing During Infection." Trends Immunol 32, no. 3 (2011): 110-6.
Viswanathan, M. B., J. D. Jeya Ananthi, and P. Sathish Kumar. "Antimicrobial Activity of Bioactive Compounds and Leaf Extracts in Jatropha Tanjorensis." Fitoterapia 83, no. 7 (2012): 1153-9.
Wei, Y. H., C. Y. Lu, H. C. Lee, C. Y. Pang, and Y. S. Ma. "Oxidative Damage and Mutation to Mitochondrial DNA and Age-Dependent Decline of Mitochondrial Respiratory Function." Ann N Y Acad Sci 854 (1998): 155-70.
Wei, Y. S., H. Zhang, X. H. Lu, Y. S. Dong, and B. H. Zhao. "[N01wa-735e, a Human Leukocyte Elastase Inhibitor from Metabolites of Microorganisms]." Sheng Wu Gong Cheng Xue Bao 23, no. 6 (2007): 1112-5.
Whitaker, B. D., and N. E. Gapper. "Ripening-Specific Stigmasterol Increase in Tomato Fruit Is Associated with Increased Sterol C-22 Desaturase (Cyp710a11) Gene Expression." J Agric Food Chem 56, no. 10 (2008): 3828-35.
Williams, J. A., and E. Shacter. "Regulation of Macrophage Cytokine Production by Prostaglandin E2. Distinct Roles of Cyclooxygenase-1 and -2." J Biol Chem 272, no. 41 (1997): 25693-9.
Yazdi, A. S., G. Guarda, N. Riteau, S. K. Drexler, A. Tardivel, I. Couillin, and J. Tschopp. "Nanoparticles Activate the Nlr Pyrin Domain Containing 3 (Nlrp3) Inflammasome and Cause Pulmonary Inflammation through Release of Il-1alpha and Il-1beta." Proc Natl Acad Sci U S A 107, no. 45 (2010): 19449-54.

Ye, Z., and J. P. Ting. "Nlr, the Nucleotide-Binding Domain Leucine-Rich Repeat Containing Gene Family." Curr Opin Immunol 20, no. 1 (2008): 3-9.
Zhao, Y., J. Yang, J. Shi, Y. N. Gong, Q. Lu, H. Xu, L. Liu, and F. Shao. "The Nlrc4 Inflammasome Receptors for Bacterial Flagellin and Type Iii Secretion Apparatus." Nature 477, no. 7366 (2011): 596-600.