請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67318完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃德富(Tur-Fu Huang) | |
| dc.contributor.author | Lung-Yen Kuo | en |
| dc.contributor.author | 郭龍彥 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:27:41Z | - |
| dc.date.available | 2017-09-13 | |
| dc.date.copyright | 2017-09-13 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-07 | |
| dc.identifier.citation | Aaronson, D. S., & Horvath, C. M. (2002). A road map for those who don't know JAK-STAT. Science, 296(5573), 1653-1655. doi:10.1126/science.1071545
Achar, K. C., Hosamani, K. M., & Seetharamareddy, H. R. (2010). In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur J Med Chem, 45(5), 2048-2054. doi:10.1016/j.ejmech.2010.01.029 Aggarwal, B. B. (2003). Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol, 3(9), 745-756. doi:10.1038/nri1184 Akira, S., & Takeda, K. (2004). Toll-like receptor signalling. Nat Rev Immunol, 4(7), 499-511. doi:10.1038/nri1391 Alexander, C., & Rietschel, E. T. (2001). Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res, 7(3), 167-202. Alves-Rosa, F., Vulcano, M., Beigier-Bompadre, M., Fernandez, G., Palermo, M., & Isturiz, M. A. (2002). Interleukin-1beta induces in vivo tolerance to lipopolysaccharide in mice. Clin Exp Immunol, 128(2), 221-228. Angus, D. C., & van der Poll, T. (2013). Severe sepsis and septic shock. N Engl J Med, 369(21), 2063. doi:10.1056/NEJMc1312359 Arango Duque, G., & Descoteaux, A. (2014). Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol, 5, 491. doi:10.3389/fimmu.2014.00491 Ashley, N. T., Weil, Z. M., & Nelson, R. J. (2012). Inflammation: Mechanisms, Costs, and Natural Variation. Annual Review of Ecology, Evolution, and Systematics, 43(1), 385-406. doi:10.1146/annurev-ecolsys-040212-092530 Banerjee, S., Biehl, A., Gadina, M., Hasni, S., & Schwartz, D. M. (2017). JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs, 77(5), 521-546. doi:10.1007/s40265-017-0701-9 Bone, R. C. (1991). Sepsis syndrome. New insights into its pathogenesis and treatment. Infect Dis Clin North Am, 5(4), 793-805. Bukhari, S. N., Lauro, G., Jantan, I., Fei Chee, C., Amjad, M. W., Bifulco, G., . . . Rahman, N. A. (2016). Anti-inflammatory trends of new benzimidazole derivatives. Future Med Chem, 8(16), 1953-1967. doi:10.4155/fmc-2016-0062 Castellheim, A., Brekke, O. L., Espevik, T., Harboe, M., & Mollnes, T. E. (2009). Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol, 69(6), 479-491. doi:10.1111/j.1365-3083.2009.02255.x Chang, C. Y., Tucci, M., & Baker, R. C. (2000). Lipopolysaccharide-stimulated nitric oxide production and inhibition of cell proliferation is antagonized by ethanol in a clonal macrophage cell line. Alcohol, 20(1), 37-43. Cohen, J. (2002). The immunopathogenesis of sepsis. Nature, 420(6917), 885-891. doi:10.1038/nature01326 Coskun, M., Salem, M., Pedersen, J., & Nielsen, O. H. (2013). Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res, 76, 1-8. doi:10.1016/j.phrs.2013.06.007 Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860-867. doi:10.1038/nature01322 Crosswhite, P., & Sun, Z. (2010). Nitric oxide, oxidative stress and inflammation in pulmonary arterial hypertension. J Hypertens, 28(2), 201-212. doi:10.1097/HJH.0b013e328332bcdb Dinarello, C. A. (2010). Anti-inflammatory Agents: Present and Future. Cell, 140(6), 935-950. doi:10.1016/j.cell.2010.02.043 Fitzgerald, G. A. (2004). Coxibs and cardiovascular disease. N Engl J Med, 351(17), 1709-1711. doi:10.1056/NEJMp048288 Forstermann, U., & Sessa, W. C. (2012). Nitric oxide synthases: regulation and function. Eur Heart J, 33(7), 829-837, 837a-837d. doi:10.1093/eurheartj/ehr304 Freeman, B. D., & Natanson, C. (2000). Anti-inflammatory therapies in sepsis and septic shock. Expert Opin Investig Drugs, 9(7), 1651-1663. doi:10.1517/13543784.9.7.1651 Ghosh, S., May, M. J., & Kopp, E. B. (1998). NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol, 16, 225-260. doi:10.1146/annurev.immunol.16.1.225 Gordon, S., & Taylor, P. R. (2005). Monocyte and macrophage heterogeneity. Nat Rev Immunol, 5(12), 953-964. doi:10.1038/nri1733 Greenhill, C. J., Rose-John, S., Lissilaa, R., Ferlin, W., Ernst, M., Hertzog, P. J., . . . Jenkins, B. J. (2011). IL-6 trans-signaling modulates TLR4-dependent inflammatory responses via STAT3. J Immunol, 186(2), 1199-1208. doi:10.4049/jimmunol.1002971 Harris, W. S., & Von Schacky, C. (2004). The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med, 39(1), 212-220. doi:10.1016/j.ypmed.2004.02.030 Herrera-Velit, P., & Reiner, N. E. (1996). Bacterial lipopolysaccharide induces the association and coordinate activation of p53/56lyn and phosphatidylinositol 3-kinase in human monocytes. J Immunol, 156(3), 1157-1165. Hommes, D. W., Peppelenbosch, M. P., & van Deventer, S. J. (2003). Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut, 52(1), 144-151. Huang, S. W., Kuo, H. L., Hsu, M. T., Tseng, Y. J., Lin, S. W., Kuo, S. C., . . . Huang, T. F. (2016). A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models. Thromb Haemost, 116(2), 285-299. doi:10.1160/TH15-12-0993 Ialenti, A., Ianaro, A., Moncada, S., & Di Rosa, M. (1992). Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol, 211(2), 177-182. Jatiani, S. S., Baker, S. J., Silverman, L. R., & Reddy, E. P. (2010). Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer, 1(10), 979-993. doi:10.1177/1947601910397187 Johnson, G. L., & Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 298(5600), 1911-1912. doi:10.1126/science.1072682 Kaplan, M. H. (2013). STAT signaling in inflammation. JAKSTAT, 2(1), e24198. doi:10.4161/jkst.24198 Kimura, A., Naka, T., Muta, T., Takeuchi, O., Akira, S., Kawase, I., & Kishimoto, T. (2005). Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT. Proc Natl Acad Sci U S A, 102(47), 17089-17094. doi:10.1073/pnas.0508517102 Kleinert, H., Schwarz, P. M., & Forstermann, U. (2003). Regulation of the expression of inducible nitric oxide synthase. Biol Chem, 384(10-11), 1343-1364. doi:10.1515/BC.2003.152 Kumar, H., Kawai, T., & Akira, S. (2009). Toll-like receptors and innate immunity. Biochem Biophys Res Commun, 388(4), 621-625. doi:10.1016/j.bbrc.2009.08.062 Kurumbail, R. G., Stevens, A. M., Gierse, J. K., McDonald, J. J., Stegeman, R. A., Pak, J. Y., . . . Stallings, W. C. (1996). Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 384(6610), 644-648. doi:10.1038/384644a0 Lawrence, T. (2009). The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 1(6), a001651. doi:10.1101/cshperspect.a001651 Lawrence, T., & Gilroy, D. W. (2007). Chronic inflammation: a failure of resolution? Int J Exp Pathol, 88(2), 85-94. doi:10.1111/j.1365-2613.2006.00507.x Lehmann, V., Freudenberg, M. A., & Galanos, C. (1987). Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med, 165(3), 657-663. Li, H., Horke, S., & Forstermann, U. (2014). Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis, 237(1), 208-219. doi:10.1016/j.atherosclerosis.2014.09.001 Li, Q., & Verma, I. M. (2002). NF-kappaB regulation in the immune system. Nat Rev Immunol, 2(10), 725-734. doi:10.1038/nri910 Liang, Y., Zhou, Y., & Shen, P. (2004). NF-kappaB and its regulation on the immune system. Cell Mol Immunol, 1(5), 343-350. Lu, Y. C., Yeh, W. C., & Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine, 42(2), 145-151. doi:10.1016/j.cyto.2008.01.006 Luiking, Y. C., Engelen, M. P., & Deutz, N. E. (2010). Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care, 13(1), 97-104. doi:10.1097/MCO.0b013e328332f99d Marienfeld, R., Neumann, M., Chuvpilo, S., Escher, C., Kneitz, B., Avots, A., . . . Serfling, E. (1997). Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells. Eur J Immunol, 27(7), 1601-1609. doi:10.1002/eji.1830270703 Maroon, J. C., Bost, J. W., & Maroon, A. (2010). Natural anti-inflammatory agents for pain relief. Surg Neurol Int, 1, 80. doi:10.4103/2152-7806.73804 Mayoral, R., Fernandez-Martinez, A., Bosca, L., & Martin-Sanz, P. (2005). Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells. Carcinogenesis, 26(4), 753-761. doi:10.1093/carcin/bgi022 Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454(7203), 428-435. doi:10.1038/nature07201 Mitchell, J. A., & Warner, T. D. (2006). COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat Rev Drug Discov, 5(1), 75-86. doi:10.1038/nrd1929 Miyake, K. (2004). Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol, 12(4), 186-192. doi:10.1016/j.tim.2004.02.009 Mogensen, T. H. (2009). Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev, 22(2), 240-273, Table of Contents. doi:10.1128/CMR.00046-08 Moncada, S., & Higgs, A. (1993). The L-arginine-nitric oxide pathway. N Engl J Med, 329(27), 2002-2012. doi:10.1056/NEJM199312303292706 Morrison, D. C., & Ryan, J. L. (1987). Endotoxins and disease mechanisms. Annu Rev Med, 38, 417-432. doi:10.1146/annurev.me.38.020187.002221 Nathan, C. (2002). Points of control in inflammation. Nature, 420(6917), 846-852. doi:10.1038/nature01320 Nelson, A. B., Lau, B. H., Ide, N., & Rong, Y. (1998). Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage. Drug Dev Ind Pharm, 24(2), 139-144. doi:10.3109/03639049809085598 Nishimoto, N., & Kishimoto, T. (2004). Inhibition of IL-6 for the treatment of inflammatory diseases. Curr Opin Pharmacol, 4(4), 386-391. doi:10.1016/j.coph.2004.03.005 Nishimoto, N., & Kishimoto, T. (2006). Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol, 2(11), 619-626. doi:10.1038/ncprheum0338 Okugawa, S., Ota, Y., Kitazawa, T., Nakayama, K., Yanagimoto, S., Tsukada, K., . . . Kimura, S. (2003). Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages. Am J Physiol Cell Physiol, 285(2), C399-408. doi:10.1152/ajpcell.00026.2003 Park, E. J., Kim, S. A., Choi, Y. M., Kwon, H. K., Shim, W., Lee, G., & Choi, S. (2011). Capric acid inhibits NO production and STAT3 activation during LPS-induced osteoclastogenesis. PLoS One, 6(11), e27739. doi:10.1371/journal.pone.0027739 Parrillo, J. E. (1993). Pathogenetic mechanisms of septic shock. N Engl J Med, 328(20), 1471-1477. doi:10.1056/NEJM199305203282008 Pearson, G., Robinson, F., Beers Gibson, T., Xu, B. E., Karandikar, M., Berman, K., & Cobb, M. H. (2001). Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev, 22(2), 153-183. doi:10.1210/edrv.22.2.0428 Ramachandran, G. (2014). Gram-positive and gram-negative bacterial toxins in sepsis: a brief review. Virulence, 5(1), 213-218. doi:10.4161/viru.27024 Rawlings, J. S., Rosler, K. M., & Harrison, D. A. (2004). The JAK/STAT signaling pathway. J Cell Sci, 117(Pt 8), 1281-1283. doi:10.1242/jcs.00963 Rehman, Q., & Sack, K. E. (1999). When to try COX-2-specific inhibitors. Safer than standard NSAIDs in some situations. Postgrad Med, 106(4), 95-97, 101-102, 105-106. doi:10.3810/pgm.1999.10.1.704 Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol, 31(5), 986-1000. doi:10.1161/ATVBAHA.110.207449 Rincon, M. (2012). Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol, 33(11), 571-577. doi:10.1016/j.it.2012.07.003 Sabio, G., & Davis, R. J. (2014). TNF and MAP kinase signalling pathways. Semin Immunol, 26(3), 237-245. doi:10.1016/j.smim.2014.02.009 Sheng, Y., Pero, R. W., Amiri, A., & Bryngelsson, C. (1998). Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Anticancer Res, 18(5A), 3363-3368. Taylor, P. C., & Feldmann, M. (2009). Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol, 5(10), 578-582. doi:10.1038/nrrheum.2009.181 Toussaint, S., & Gerlach, H. (2009). Activated protein C for sepsis. N Engl J Med, 361(27), 2646-2652. doi:10.1056/NEJMct0808063 Vane, J., & Botting, R. (1987). Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J, 1(2), 89-96. Villarino, A. V., Kanno, Y., Ferdinand, J. R., & O'Shea, J. J. (2015). Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol, 194(1), 21-27. doi:10.4049/jimmunol.1401867 Wilkins, M. R., Wharton, J., Grimminger, F., & Ghofrani, H. A. (2008). Phosphodiesterase inhibitors for the treatment of pulmonary hypertension. Eur Respir J, 32(1), 198-209. doi:10.1183/09031936.00124007 Yoshimura, A., Naka, T., & Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol, 7(6), 454-465. doi:10.1038/nri2093 Zhao, J., Yu, H., Liu, Y., Gibson, S. A., Yan, Z., Xu, X., . . . Qin, H. (2016). Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol, 311(5), L868-L880. doi:10.1152/ajplung.00281.2016 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67318 | - |
| dc.description.abstract | 發炎反應(Inflammation)為組織受傷或受生物侵入時，體內所產生的自然防禦機制，一般具有紅、熱、腫、痛的症狀，會引起微血管擴張、血流加速、血管通透性增加並促使白血球轉移至發炎部位，進而吞噬病原體以及受傷組織。在發炎反應的過程中，活化的免疫細胞還會分泌多種具有細胞毒殺作用或促進發炎反應活化的細胞激素(pre-inflammatory cytokine)來維持或增強發炎反應的進行以助於個體清除外來的有害刺激；然而，過度的發炎反應會造成個體的傷害，並觸發多種和發炎反應相關的疾病，例如：關節炎、多發性硬化症、氣喘、動脈硬化、自體免疫疾病、癌症、阿茲海默症以及急性敗血症。因此尋找具有抗發炎活性的藥物用以抑制過度的發炎反應成為現今藥物開發的重要方向。
在初步的藥物篩選過程中，我們發現nstbpb5185的衍生物， pre-LBK0具有抗發炎活性。且在活性測試的劑量下，不會影響細胞的存活率。化合物pre-LBK02在30 microM時即可有效抑制受細菌內毒素(LPS)活化的鼠源巨噬細胞或人類的單核細胞所分泌的細胞激素， TNF-alpha和IL-6並且同時降低NO的產生。此外我們也使用了敗血症動物模式來探究pre-LBK02對於急性發炎的動物是否有抗發炎活性，我們發現pre-LBK02可以有效地降低發炎引發之病理反應，如降低敗血症小鼠血清中的發炎細胞激素，改善敗血症小鼠所受到的器官損傷。 在作用機制的探討方面，我們發現給予pre-LBK02後，對於抑制LPS所產生的下游訊息傳遞鏈主要以抑制MAPK、NF-kappaB、JAKs/STATs的活化為主。在MAPK活化路徑中，我們檢視了三種激酶ERK1/2、JNK、p38的磷酸化現象，發現化合物pre-LBK02對於三種激酶都有抑制作用；另外也檢視了NF-kappaB活化路徑的重要因子：I-kappa-B-alpha的磷酸化以及降解情形，發現化合物pre-LBK02能抑制I-kappa-B-alpha磷酸化和降解現象；pre-LBK02也可從轉錄層級去抑制NF-kappaB活化路徑下游產生的酵素像是iNOS、COX-2的表現。此外，我們也發現，pre-LBK02也能減少某些跟發炎反應相關的JAKs/STATs的活化(JAK2、STAT5、STAT3)。綜合上述結果，我們認為pre-LBK02是藉由抑制MAPK、NF-kappaB、JAKs/STATs的活化來達到抑制發炎反應的效果。 | zh_TW |
| dc.description.abstract | Inflammation, usually characterized by swelling, redness, pain and heat, is a crucial function of the innate immune system for protecting the host against pathogens. Upon bacteria invasion, mammalian monocytes/ macrophages release a variety of inflammatory mediators such as pro-inflammatory and cytotoxic cytokines, nitric oxide and reactive oxygen species to defense harmful stimuli, but excessive inflammatory reaction leads to extensive tissue damage and manifestation of pathological states such as multiple sclerosis, asthma, arthritis, atherosclerosis, Alzheumer’s disease and cancer. Hence, targeting on uncontrolled inflammation seems feasible to control numerous inflammation-associated diseases.
Under the drug screening process of nstpbp5185 derivatives, we discovered that compound pre-LBK02, a synthetic benzimidazole molecule, possessed anti-inflammatory effects in decreasing the release of pro-inflammatory cytokines including TNF-alpha and IL-6, as well as decreased the production of NO, and we also excluded its cytotoxicity by cell viability and LDH assay. Furthermore, we found that pre-LBK02 attenuates some pathological syndromes of LPS-induced endotoxemia in mice, such as decreasing the cytokine release, protecting the mice from tissue injury in septic conditions. These results suggest the beneficial effects of pre-LBK02 in septic animal models. Regarding protein expression of LPS-stimulated RAW264.7 cells, we observed that the molecular mechanism of pre-LBK02-mediated anti-inflammation is associated with decreasing phosphorylation of MAP kinases such as ERK1/2, JNK and p38. pre-LBK02 also inhibited phosphorylation of Ikappa B alpha and reversed Ikappa B alpha degradation and attenuated the expression of NF-kappaB-related downstream inducible enzymes such as iNOS and COX-2. In addition, we also identified that pre-LBK02 might be a potential anti-inflammatory agent by downregulating phosphorylation of some JAKs/STATs associated with inflammation such as JAK2, STAT5, STAT3. Taken together, these results indicate that pre-LBK02 inhibits LPS-induced inflammation by inhibiting phosphorylation of MAP kinases and Ikappa B alpha and downregulating phosphorylation of some JAKs/STATs. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:27:41Z (GMT). No. of bitstreams: 1 ntu-106-R04443009-1.pdf: 9745991 bytes, checksum: 4a0d56f912c67ef7c7754c9af5352362 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 目 錄
口委審定書 I 誌謝 II 中文摘要 IV Abstract VI 目 錄 VIII Figures XII Table XIV Abbreviation table XV CHAPTER 1 1 1.1 Inflammation 1 1.2 Monocytes and macrophages 3 1.3 Macrophage-derived cytotoxic and pro-inflammatory mediators 5 1.3.1 Cytokines 5 1.3.2 Nitric oxide (NO) 9 1.3.3 Cyclooxygenase-2 (COX-2) 13 1.4 Signaling pathways of lipopolysaccharide (LPS) 14 1.4.1 Toll-like receptors (TLRs) 16 1.4.2 Mitogen-activated protein (MAP) kinase pathway 16 1.4.3 NF-B pathway 18 1.4.4 JAK-STAT signaling 21 1.5 Severe Sepsis and Septic Shock 23 1.6 Aim of this study 26 CHAPTER2 45 2.1 Materials 45 2.2 Cell cultures 46 2.2.1 Cell culture - RAW264.7 cell 46 2.2.2 Cell- culture – Human THP-1 monocyte 46 2.3 Cell viability assay 46 2.4 LDH assay 47 2.5 Nitric oxide assay 48 2.6 Cytokine assays 49 2.7 Subcellular fractionation 50 2.8 Western blot analysis 50 2.9 In vivo assay (Animal model) 52 2.9.1 Animals 52 2.9.2 LPS challenge 52 2.9.3 Mice whole blood and serum collection 52 2.9.4 Measurement of cytokine levels 53 2.9.5 Histological examination 53 2.10 Stastistical analysis 53 CHAPTER 3 55 3.1 The exploration of anti-inflammatory compounds from ntspbp5185-derivatives 55 3.2 pre-LBK02 inhibits LPS-induced TNF-alpha and IL-6 production in LPS-stimulated RAW264.7 cells 55 3.3 The effects of pre-LBK02 on cell cytotoxicity on RAW264.7 cells 56 3.4 The effects of pre-LBK02 on cell integrity of RAW264.7 cells 57 3.5 pre-LBK02 preferentially inhibits IL-6 release rather than TNF-alpha in LPS-stimulated RAW264.7 cells 57 3.6 pre-LBK02 inhibits nitric oxide production in LPS-stimulated RAW264.7 cells 59 3.7 pre-LBK02 inhibits COX-2 expression in LPS-stimulated RAW264.7 cells 60 3.8 pre-LBK02 inhibits phosphorylation of MAPKs in LPS-stimulated RAW264.7 cells 60 3.9 pre-LBK02 inhibits I kappa B alpha degradation in LPS-stimulated RAW264.7 cells 61 3.10 pre-LBK02 inhibiting IL-6 production might be due to downregulating the phosphorylation of JAKs/STATs molecules in LPS-stimulated RAW264.7 cells 62 3.11 The effects of pre-LBK02 on LPS-challenged endotoxemia in vivo 64 3.11.1 pre-LBK02 inhibits pro-inflammatory cytokines production including TNF-alpha and IL-6 and prolonged the survival in LPS-challenged endotoxemia in vivo 65 3.11.2 Effects of pre-LBK02 on tissue injury in endotoxemia examined by histochamistry 65 3.12 pre-LBK02 inhibits LPS-induced TNF-alpha and IL-6 production in LPS-stimulated human THP-1 monocytes 66 CHAPTER 4 87 CHAPTER5 98 Reference 100 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抗發炎作用 | zh_TW |
| dc.subject | 化合物pre-LBK02 | zh_TW |
| dc.subject | compound pre-LBK02 | en |
| dc.subject | anti-inflammatory | en |
| dc.title | 化合物pre-LBK02之抗發炎作用及機轉之探討 | zh_TW |
| dc.title | The anti-inflammatory effects and mechanisms of compound pre-LBK02 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 顏茂雄(Mao-Hsiung Yen),鄧哲明(Che-Ming Teng),楊春茂(Chuen-Mao Yang),吳文彬(Wen-Bin Wu) | |
| dc.subject.keyword | 抗發炎作用,化合物pre-LBK02, | zh_TW |
| dc.subject.keyword | anti-inflammatory,compound pre-LBK02, | en |
| dc.relation.page | 105 | |
| dc.identifier.doi | 10.6342/NTU201702325 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-07 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 9.52 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。