敗血症是由細菌感染所引起的全身性發反應症之臨床症狀，其會造成多重器官傷害，且擁有極高的死亡率。革蘭氏陰性菌的細胞壁成分酯多醣體，是巨噬細胞的強力活化物，在敗血症中扮演了相當重要的角色。根據先前研究，芝麻酚在以酯多醣體誘導之敗血症動物模式中，具有保護作用，並且有效降低了發炎反應，但其機制仍然不清楚。因此，本研究的目標為探討芝麻酚對於內毒素引起的巨噬細胞發炎物質釋放造成之影響與其可能的機制。結果顯示，芝麻酚隨處理濃度的增加，明顯抑制前發炎物質，腫瘤壞死因子-a、介白質-1b與一氧化氮的產生並且抑制誘導型一氧化氮合成酵素的蛋白和mRNA表現。芝麻酚抑制轉錄因子NF-kB的轉移與活化，並且增加了IkB-a抑制蛋白的表現，芝麻酚對於以介白質-1b與肽聚醣誘導的一氧化氮生成，也有抑制其生成的作用，但無法抑制腫瘤壞死因子-a誘導的一氧化氮釋放。綜合以上結果，芝麻酚可能經由干擾toll/IL-1接受體的訊號傳遞，對酯多醣體造成的前發炎物質釋放有抑制的作用。

Sepsis, mainly caused by bacteria-induced systemic inflammation, is the top 13 cause of death in Taiwan. Lipopolysaccharide (LPS), a component of Gram-negative bac-terial cell wall, has been reported to play an important role in the pathogenesis of sep-sis. Sesamol attenuates inflammation and increases the survival rate in LPS-challanged rats; however, the exact mechanism is obscured. The aim of this study was to investi-gate the mechanism underlying the anti-inflammatory effect of sesamol in LPS-stimulated primary macrophages. Sesamol (a) inhibited tumour necrosis factor-a, in-terleukin-1b, and nitrite production in LPS-treated macrophages; (b) decreased the protein and mRNA expressions of inducible nitric oxide synthase; (c) reduced tran-scription factor nuclear factor-kB translocation and DNA binding activity, and (d) increased inhibitor kB expression; and (e) decreased nitrite production induced by interleukin-1b or peptidoglycan, but not tumor necrosis factor-a. In conclusion, sesamol might reduce LPS-stimulated pro-inflammatory mediators release by interfer-ing toll/interleukin-1 receptor signaling pathway in primary peritoneal macrophages.

Abraham E. NF-kappaB activation. Crit Care Med 28:N100-N104, 2000.
Acton RD, Dahlberg PS, Uknis ME, Klaerner HG, Fink GS, Norman JG, Dunn DL. Differential sensitivity to Escherichia coli infection in mice lacking tumor necrosis factor p55 or interleukin-1 p80 receptors. Arch Surg 131:1216-1221, 1996.
Aigner T, Soeder S, Haag J. IL-1beta and BMPs--interactive players of cartilage matrix degradation and regeneration. Eur Cell Mater 12:49-56, 2006.
Akira S and Takeda K. Toll-like receptor signaling. Nature Rev 4:499-511, 2004.
Akira S, Hoshino K, Kaisho T. The rele of Toll-like receptors and MyD88 in innate immune response. J Endotoxin Res 6:383-387, 2000.
Angus DC, Birmingham MC, Balk RA, Scannon PJ, Collins D, Kruse JA, Graham DR, Dedhia HV, Homann S, Maclntyre H. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. JAMA 283:1723-1730, 2000.
Backlund U, Holm S. Treatment with NSAID can delay the diagnosis in GAS-sepsis. Lakartidningen 94:602, 1997.
Baldwin AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649-683, 1996.
Baumgartner JD. Monoclonal anti-endotoxin antibodies for the treatment of Gram-negative bacteremia and septic shock. Eur J Clin Microbiol Infect Dis 9:711-716, 1990.
Beck GCH, Brinkkoetter P, Hanusch C, Schulte J, van Ackern K, van der Woude FJ, Yard BA. Clinical review: immunomodulatory effects of dopamine in general in-flammation. Crit Care 8:485-491, 2004.
Bellingan G. Inflammatory cell activation in sepsis. Br Med Bull 55:12-29, 1999.
Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ. Efficacy and safty of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709, 2001.
Beutler B, Milsark IW, and Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869-871, 1985.
Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869-871, 1985.
Bhakdi S, Walev I, Jonas D, Plamr M, Weller U, Suttorp N, Grimminger F, Seeger W. Pathogenesis of sepsis syndrome: possible relevance of pore-forming bacterial toxins. Curr Top Microbiol Immunol 216:101-118, 1996.
Bianchini A, Monserrat JM. Effects of methyl parathion on Chasmagnathus granulatus hepatopancreas: protective role of sesamol. Ecotoxicol Environ Saf 67:100-108, 2007.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions of sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/ Society of Critical Care Medicine. Chest 101:1644-1655, 1992.
Bone RC. Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med 24:163-172, 1996.
Bosshart H, Heinzelmann M. Targeting bacterial endotoxin: two side of a coin. Ann N Y Acad Sci 1096:1-17, 2007.
Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 119:1198-1208, 1993.
Bowie A, O'Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 67:508-514, 2000.
Brouckaert P, Fiers W. Tumor necrosis factor and the systemic inflammatory response syndrome. Curr Top Microbiol Immunol 216:167-182, 1996.
Charles AD. Blocking IL-1 in systemic inflammation. J Emerg Med 201:1355-1359, 2005.
Chauhan SD, Seggara G, Vo PA, Macallister RJ, Hobbs AJ, Ahluwalia A. Protection against lipopolysaccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice. FASEB J 17:733-775, 2003.
Clark MA, Plank LD, Connolly AB, Streat SJ, Hill AA, Gupta R, Monk DN, Shenkin A, Hill GL. Effect of a chimeric antibody to tumor necrosis factor-α on cytokine and physiologic responses in patients with severe sepsis-a randomized, clinical trial. Crit Care Med 26:1650-1659, 1998.
Cohen J, Glauser MP. Septic shock: treatment. Lancet 338:736-739, 1991.
Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ. Corticoste-roid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23:1430-1439, 1995.
De kimpe SJ, Kengatharan M, Thiemermann C, Vane JR. The cell wall components pepetidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci 92:10359-10363, 1995.
Di padova FE, Brade H, Barclay GR, Poxton IR, Liehl E, Schuetze E, Kocher HP, Ramsay G, Schrier MH, McClellaland DBL, Rietschel ET. A broadly cross-recative monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides. Infect Immunol 61:3863-3872, 1993.
Dinarello CA. Blocking IL-1 in systemic inflammation. J Exp Med 201:1355-1359, 2005.
Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 10:201-222, 2004.
Fibbe WE, van Damme J, Billiau A, Voogt PJ, Duinkerken N, Kluck PM, Falkenburg JH. Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood 68:1316-1321, 1986.
Fishe CJ, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fu-sion protein. N Engl J Med 334:1697-1702, 1996.
Flores EA, Bistrian BR, Pomposelli JJ, Dinarello CA, Blackburn GL, Istfan NW. Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin 1. J Clin Invest 83:1614-1622, 1989.
Friedman GSE and Vicent JL. Has the mortality of septic shock changed with time. Crit Care Med 26:2078-2086, 1998.
Fukuda Y, Osawa T, Kawakishi S, Namiki M. Chemistry of lignan antioxidants in sesame seeds and oil. Food phytochemicals for cancer prevention II. Teas, spices and herbs. In: Food phytochemicals for cancer prevention II ACS symposium series. American Chemical Soc 547:264–274, 1994.
Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 109:S81-S96, 2002.
Ghosh S, May MJ, Kopp EB. NF-B and Rel proteins: evolutionarily conserved media-tors of immuno responses. Ann Rev Immunol 16:225-260, 1998.
Gibson FC, Onderdonk AB, Kasper DL, Tzianabos AO. Cellular mechanism of intraaab-dominal abscess formation by Bacteroides fragilis. J Immunol 160:5000-5006, 1998.
Green LC, Ruiz de Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannen-baum SR. Nitrate biosynthesis in man. Proc Natl Acad Sci USA 78:7764-7768, 1981.
Greenman RL, Schein RMH, Martin MA, Wenzel RP, MacIntyre NR, Emmanuel G, Chmel H, Kohler RB, McCarthy M, Plouffe J, Russell JA. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA 266:1097-1102, 1991.
Griffith OW, Stuehr DJ. Nitric oxide synthase: properties and catalytic mechanism. Ann Rev Physiol 57:707-736, 1995.
Hayden MS and Ghosh S. Signaling to NF-kappa B. Gene Dev 18:2195-2224, 2004.
Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J, Stewart CL, Goyert SM. Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 4:407–414, 1996.
Heba G, Krzeminski T, Proc M, Grzyb J, Dembinska-Kiec A. Relation between expres-sion of TNF alpha, iNOS, VEGF mRNA and development of heart failure after expe-rimental myocardial infarction in rats. J Physiol Pharamacol 52:39-52, 2001.
Hellman J, Loiselle PM, Tehan MM, Allaire JE, Boyle LA, Kurnick JT, Andrews DM, Sik KK, Warren HS. Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum. Infect. Immun 68:2566-2572, 2000.
Hellman J, Loiselle PM, Zanzot EM, Allaire JE, Tehan MM, Boyle LA. Release of gram-negative outer-membrane proteins into human serum and septic rat blood and their interactions with immunoglobulin in antiserum to Escherichia coli J5. J Infect Dis 181:1034-1043, 2005.
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 408:740-745, 2000.
Henderson B, Pettipher ER. Arthritogenic actions of recombinant IL-1 and tumor necro-sis factor-alpha in rabbit: evidence for synergistic interactions between cytokines in vivo. Clin Exp Immunol 75:306-310, 1989.
Hiemstra PS, Eisenhauer PB, Harwig SSL, Van Den Barselaar MT, Van Furth R, and Lehrer RI. Antimicrobial proteins of murine macrophages. Infect. Immun 61:3038-3046, 1993.
Hollenberg SM, Broussard M, Osman J, Parrillo JE. Increased microvasscular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase. Circ Res 86:774-778, 2000.
Hori T, Nakashima T, Take S, Kaizuka Y, Mori T, Katafuchi T. Immune cytokines and regulation of body temperature, food intake and cellular immunity. Brain Res Bull 27:309-313, 1991.
Horn KD. Evolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS). Q J Med 91:265-277, 1998.
Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S. Cutting edge: toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopo-lysaccharide: evidence for TLR4 as the LPS gene product. J immunol 162: 3749-3752, 1999.
Hsu DZ, Chen KT, Li YH, Chuang YC, Liu MY. Sesamol delay mortality and attenuates hepatic injury after cecal ligation and puncture in rats: role of oxidative stress. Shock 25:528-532, 2006b.
Hsu DZ, Li YH, Chu PY, Chien SP, Chuang YC, Liu MY. Attenuation of endotoxin-induced oxidative stress and multiple organ injury by 3,4-Methylenedioxyphenal in rats. Shock 25:300-305, 2006a.
Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4:387-396, 1996a.
Hsu H, Shu HB, Pan MG, Goeddel DV. TRADD-TRAF-2 and TRADD-FADD interac-tions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299-308, 1996b.
Ignarro LJ. Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol 53:503-514, 2002.
Iwami, K., T. Matsuguchi, A. Masuda, T. Kikuchi, T. Musikacharoen, and Y. Yoshikai. 2000. Cutting edge: naturally occurring soluble form of mouse toll-like receptor 4 in-hibits lipopolysaccharide signaling. J Immunol 165:6682-6686.
Janeway CA, Travers P, Walport M, Shlolomchik MJ. Immunobiology. Churchill living-stone 12-13, 2005.
Jinbo T, Sakamoto T, Yamamoto S. Serum alpha2-macroglobin and cytokine measure-ments in an acute inflammation model in rats. Lab Anim 36:153-157,2002.
Jung CH, Kim JH, Hong MH, Seog HM, Oh SH, Lee PJ, Kim GJ, Kim HM, Um JY, Ko SG. Phenolic-rich fraction from Rhus verniciflua Stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW264.7 macrophages. J of Ethnopharmacology 110:490-497, 2007.
Kapadia GJ, Azuine MA, Tokuda H, Takasaki M, Mukainaka T, Konoshima T, Nishino H. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis. Pharmacol Res 45:499-505, 2002.
Karin M and Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-kappa B activity. Annu Rev Immunol 18: 621-663, 2000.
Kaur IP, Saini A. Sesamol exhibits antimutagenic activity against oxygen species me-diated mutagenicity. Mutat Res 2000; 470: 71–76.
Kim JY, Choi DS, Jung MY. Antiphoto-oxidative activity of sesamol in methylene blue- and chlorophyll-sensitized photo-oxidation of oil. J Agric Food Chem 51:3460-3465, 2003.
Kleinert H, Pautz A, Linker K, Schwarz PM. Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500:255-266, 2004.
Knuefermann P, Nemoto S, Misra A, Nozaki N, Defreitas G, Goyert SM, Carabello BA, Mann DL, Vallejo JG. CD14-deficient mice are protected against lipopolysaccharide-induced cardiac inflammation and left ventricular dysfunction. Circulation 106:2608–2615, 2002.
Kristof AS, Goldberg P, Laubach V, Hussain SN. Role of inducible nitric oxide synthase in endotoxin-induced acute lung injury. Am J Respir Crit Care Med 158:1883-1889, 1998.
Lander HM, Sehajpal P, Levine DM, Novogrodsky A. Activation of human peripheral blood mononuclear cells by nitric oxide-generating compound. J Immunol 150:1509-1516, 1993.
Lefering R, Neugebauer EA. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 23:1294-1303, 1995.
Lenk H, Tanneberger S, Muller U, Ebert J, Shiga T. Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 24:391-392, 1989.
Lien E, Means TK, Heine H, Yoshimura A, Kusumoto S, Fukase K, Fenton MJ, Oikawa M, Qureshi N, Monks B, Finberg RW, Ingalls RR, Golenbock DT. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipoppolysaccharide. J Clin Invest 105: 497-504, 2000.
Lin MW, Tsao LT, Chang LC, Chen YL, Huang LJ, Kuo SC, Tzeng CC, Lee MR, Wang JP. Inhibition of lipopolysaccharide-stimulated NO production by a novel synthetic compound CYL-4d in RAW264.7 macrophages involving the blockade of MEK4/JNK/AP-1 pathway. Biochemical Pharmacol 73:1796-1806, 2007.
Lin WJ and Yeh WC. Implication of toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24:206-209, 2005.
Liu SF, Malik AB. NF-kB activation as a pathological mechanism of septic shock and inflammation. Am J Physoiol Lung Cell Mol Physiol 290:622-645, 2006.
Lopez-Bojorquez LN, Dehesa AZ, Reyes-Teran G. Molecular mechanisms involved in the pathogenesis of septic shock. Arch Med Res 35:465-479, 2004.
MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Ann Rev Immunol 15:323-350, 1997.
Maitra SR, Wojnar MM, Lang CH. Alterations in tissue glucose uptake during the hyperglycemic and hypoglycemic phases of sepsis. Shock 13:379-385, 2000.
Marshall JC. Inflammation, coaugulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med 29:S99-S106, 2001.
Martin MU, Wesche H. Summary and comparison of the signaling mechanisms micro-vascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase. Circ Res 86:774-778, 2000.
Michel T, Feron O. Nitric oxide synthase: which, where, how, and why? J Clin Invest 100:2146-2152, 1997.
Mishra V. Oxidative stress and role of antioxidant supplementation in critical illness. Clin Lab 53:199-209, 2007.
Moncada S, Palmer RM, Higgs DA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109-142, 1992.
Moon DO, Choi YH, Kim ND, Park YM, Kim GY. Anti-inflammatory effects of beta-lapachone in lipopolysaccharide-stimulated BV2 microglia. International Immuno-pharmacology 7:506-514, 2007.
Muarry MJ. Sepsis: clinical dilemmas. Yale J Bio Med 71:485-491, 1998.
Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5:25-44, 1984.
Nathan CF. Macrophage activation: some questions. Ann Inst Pasteur Immunol 137C:345-351, 1986.
O’Neill L. The Toll/interleukin-1 receptor domain: a molecular switch for inflammation and host defence. Biochem Soc Trans 28:557-563, 2000.
Ohta S, Suzuki M, Sato N, Kamogawa A, Shinoda M. Protective effects of sesamol and its related compounds on carbon tetrachloride induced liver injury in rats. Yakugaka Zasshi 114:901–910, 1994.
Old JL. Tumor necrosis factor (TNF). Science 230:630-632, 1985.
Oldman KM, Bowen PE. Osidative stress in critical care: is antioxidant supplementation beneficial? J Am Diet Assoc 98:1001-1008, 1998.
Opal SM, Fisher CJ, Dhainaut JF, Vincent JL, Brase R, Lowry SF, Sadoff JC, Slotman GJ, Levy H, Balk RA, Shelly MP, Pribble JP, LaBrecque JF, Lookabaugh J, Donovan H, Dubin H, Baughman R, Norman J, DeMaria E, Matzel K, Abraham E, Seneff M. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, ran-domized, double-blind, placebo-controlled, multicenter trial. Crit Care Med 25:1115-1124, 1997.
Palmer RM, Ashton DS, Monacada S. Vascular endotheil cells synthesizenitric oxide from L-arginine. Nature 333:664-666, 1988.
Parihar VK, Prabhakar KR, Veerapur VP, Kumar MS, Reddy YR, Joshi R, Unnikrishnan MK, Rao CM. Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice. Mutat Res 611:9-16, 2006.
Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085-2088, 1998a.
Poltorak A, Smirnova I, He X, Liu MY, Van Huffel C, McNally O, Birdwell D, Alejos E, Silva M, Du X, Thompson P, Chan EK, Ledesma J, Roe B, Clifton S, Vogel SN, Beutler B: Genetic and physical mapping of the LPS locus: identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 24:340-355, 1998b.
Prigent M, Barlat I, Langen H, Dargemont C. IkappaBalpha and IkappaBalpha/NF-kappa B complexes are retained in the cytoplasm through interaction with a novel partner, RasGAP SH3-binding protein 2. J Biol Chem 275:36441-36449, 2000.
Qureshi ST, Gros P, Malo D. Host resistance to infection: genetic control of lipopolysac-charide responsiveness by TOLL-like receptor genes. Trends Genet 15: 291-294, 1999.
Rackow EC, Astiz ME. Pathophysiology and treatment of septic shock. JAMA 266:548-554, 1991.
Remick DG, Kunkel RG, Larrick JW, Kunkel SL. Action in vivo effects of human recombinant tumor necrosis factor. Lab Invest 56:583-590, 1987.
Remick DG, Larrick J, Kunkel SL. Tumor necrosis factor-induced alterations in circulat-ing leukocyte populations. Biochem Biophys Res Commun 141:818-824, 1986.
Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, Ulmer AJ, Zähringer U, Seydel U, Di Padova F, Schreier M, Brade H. Bacterial endotoxin: mo-lecular relationships of structure to activity and function. FASEB J 8: 217-225, 1994.
Roitt I et al. (eds.) Immunology. 5th edition, London, Mosby, 2002.
Roitt IM. Immunity to infection. Essential immunology. Blackwell Scientific Publications, 243-271, 1994.
Rothe M, Wong SC, Henzel WJ, Goeddel DV. A novel family of putative signal trans-ducers associated with the cytoplasmic domain of the 75-kDa tumor necrosis factor receptor. Cell 78:681-692, 1994.
Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 274:17406-17409, 1999.
Seibenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kappaB. Annu Rev Cell Biol 10:405-455, 1994.
Sharma S, Kaur IP. Development and evaluation of sesamol as an antiaging agent. Int J Dermatol. 45:200-208, 2006.
Sriskandan S, Evans TJ, Cohen J. Bacterial superantigen-induced human lymphocyte responses re nitric oxide dependent and mediated by IL-12 and INF- J Immunol 156:2430-35, 1996.
Stashenko P, Dewhirst FE, Peros WJ, Kent RL, Ago JM. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol 138:1464-1468, 1987.
Thanos D, Maniatis T. NF-kappaB: a lesson in family values. Cell 80:529-532, 1995.
Tracey KJ, Cerami A. Metabolic responses to cachetin/TNF-. Ann NY Acad Sci 587: 325-331, 1990.
Tracy KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kou GC, Lowry SF, Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacte-raemia. Nature 330:662-664, 1987.
Trajkovic V. Modulation of inducible nitric oxide synthase activation by immunosup-pressive drugs. Curr Drug Metab 2:315-329, 2001.
Trataglia LA, Ayres TM, Wong GH, Goeddel DV. A novel domain within the 55-kD TNF receptor signals cell death. Cell 74:845-853, 1993.
Treon SP, Anand B, Ulevitch RJ, Broitman SA. CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cyto-kine release in the treatment of AML. Leuk Res 18:17-21, 1994.
Ulevitch RJ, Tobias PS. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol 13:437-457, 1995.
Vaillancourt F, Morquette B, Shi Q, Fahmi H, Lavigne P, Di Battista JA, Fernandes JC, Benderdour M. Differential regulation of cyclooxygenase-2 and inducible nitric oxide synthase by 4-hydroxynonenal in human osteoarthritic chondrocytes through ATF-2/CREB-1 transactivation and concomitant inhibition of NF-kappaB signaling cascade. Journal of Cellular Biochemistry 100:1217-1231, 2007.
Van der Meer MJ, Sweep CG, Pesman GJ, Borm GF, Hermus AR. Synergism between IL-1beta and TNF-alpha on the activity of the pituitary-adrenal axis and on food in-take of rats. Am J Physoil 268:551-557, 1995.
Vila E, Salaices M. Cytokines and vascular reactivity in resistance arteries. Am J Physiol Heart Circ Physiol 288:1016-1021, 2005.
Waage A, Espevik T. Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J Exp Med 167:1987-1992, 1988.
Waage A, Halstensen A, Espevik T. Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1:355-357, 1987.
Wahl SM, McCartney-Francis N, Chan J, Dionne R, Ta L, Orenstein JM. Nitric oxide in experimental joint inflammation. Benefit or detriment? Cells Tissue Organs 174:26-33, 2003.
Wasserman SA. Toll signaling: the enigma variations. Curr Opin Genet Dev 10:497-502, 2000.
West NEJ, Qian HS, Guzik TJ, Black E, Cai S, George SE, Channon KM. Nitric oxide synthase (nNOS) gene transfer modifies venous bypass graft remodeling: effects on vascular smooth muscle cell differentiation and superoxide production. Circulation 104:1526-1532, 2001.
Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 340:207-214, 1999.
Xie QW, Kashiwabara Y, Nathan C. Role of transcription factor NF-B/Rel in induction of nitric oxide synthase. J Biol Chem 269:4705-4708, 1994.
Yamaguchi N, Kukita T, Li YJ, Martinez Argueta JG, Saito T, Hanazawa S, Yamashita Y. Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Ac-tinobacillus actinomycetemcomitans. FEMS Immunol Med Microbiol 49:28-34, 2007.
Yamamoto Y, Yin MJ, Lin KM, Gaynor RB. Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 274:27307-27314, 1999.
Yang J, Lin Y, Gou Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Liu Z, Su B. The essential role of MEKK3 in TNF-induced NF-B activation. Nat Immunol 2:620-624, 2001.
Zhang FX, Kirschning CJ, Mancinelli R, Xu XP, Jin Y, Faure E, Mantovani A, Rothe M, Muzio M, Aediti M. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin- signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem 274:7611-7614, 1999.