跳到主要內容

臺灣博碩士論文加值系統

(44.200.77.92) 您好!臺灣時間:2024/03/01 09:26
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:黃婉媜
研究生(外文):Huang, Wan Chen
論文名稱:第一部份:PPARg作用劑15d-PGJ2、ciglitazone、GW251929經由超氧陰離子自由基的產生活化Raf/MEK/ERK的訊息傳遞路徑第二部份:細胞激素IL-4調節LPS所引起IL-6及NO的產生經由抑制ERK、p38MAPK及PKC的訊息傳遞路徑
論文名稱(外文):Part1: Superoxide anion-dependent Raf/MEK/ERK activation by PPARg agonists 15-deoxy-D12,14-prostaglandin J2, ciglitazone and GW251929 Part2: Interleukin-4 modulates lipopolysaccharide-mediated nitric oxide and interleukin-6 release via inhibition of
指導教授:林琬琬林琬琬引用關係
指導教授(外文):Lin, Wan Wan
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:83
中文關鍵詞:過氧化小體增生活化受體轉錄活化因子脂多醣體細胞激素
外文關鍵詞:PPARgNF-kBLPSIL-4
相關次數:
  • 被引用被引用:0
  • 點閱點閱:390
  • 評分評分:
  • 下載下載:100
  • 收藏至我的研究室書目清單書目收藏:0
第一部份:
在本篇研究中,我們主要想探討三種結構不同的PPARg作用劑造成ERK活化的訊息傳遞路徑。在鼠肌纖維母細胞C2C12中,給予15d-PGJ2 ciglitazone以及GW251929會隨著時間及濃度的增加而增加ERK1/2的磷酸化作用,而同時MEK的磷酸化作用及Raf-1的活性也隨著藥物的刺激而活化。此三種PPARg作用劑所造成ERK的磷酸化作用並不會受PKC的抑制劑GF109203X及Ro31-8220抑制,也不會受PI3K的抑制劑wortmannin或Ras抑制劑FPTI影響。相反的,ERK的磷酸化作用可被MEK抑制劑PD98059,百日咳毒素pertussis toxin,及抗氧化劑所抑制。利用超微量化學發光儀偵測其產生自由基的能力,結果顯示三種作用劑都能造成超氧陰離子自由基產生,其作用程度15d-PGJ2>ciglitazone>GW251929,剛好與活化ERK的作用程度相類似。總結,在本篇研究中,我們發現三種PPARg的作用劑所造成ERK 的磷酸化作用是經由造成超氧陰離子自由基的產生及Raf/MEK/ERK的訊息傳遞路徑而來。
第二部份:
Interleukin-4 (IL-4)是ㄧ種具多功能的細胞激素,在發炎的過程中,可經由抑制發炎媒介物質的產生來抑制發炎反應的進行,而參與其中的分子機轉目前尚不清楚。在老鼠的巨噬細胞RAW 264.7中,我們發現IL-4能抑制LPS所引起NO及IL-6的產生,而這抑制作用會受PKC的抑制劑Ro31-8220,MEK的抑制劑PD98059以及p38 MAPK抑制劑SB203580所抑制,但不受PI3K的抑制劑wortmannin影響,顯示IL-4具有抑制LPS所引起PKC、ERK及p38 MAPK活性的能力。以上這些蛋白激脢在調節iNOS 及IL-6基因表現的訊息傳遞路徑中扮演重要角色。PI3K的活化當以Akt的磷酸化程度代表,在本實驗中發現同時給予LPS及IL-4的刺激對Akt的磷酸化有加成性作用。然而IL-4並不會影響LPS所引起NF-kB的活性,因為IL-4對於LPS所引起的IKK活化及IkB的分解並沒有影響。綜合以上結果:IL-4會經由抑制LPS活化PKC、ERK及p38 MAPK的活化作用,進而抑制NO及IL-6的產生。

Part I:
In this study, we examined the signaling pathways for ERK activation by three structurally different PPARg agonists. In murine C2C12 myoblasts, treatment with 15d-PGJ2, ciglitazone and GW251929 leads to ERK1/2 phosphorylation in a time- and concentration-dependent manner. Consistent with ERK phosphorylation, MEK phosphorylation as well as Raf-1 kinase activity are also accordingly stimulated. The ERK phosphorylation induced by PPARg agonists is not blocked by the PKC inhibitors GF109203X and Ro31-8220, the PI3K inhibitor wortmannin, neither the Ras inhibitor FPTI. On the contrary, the ERK phosphorylation by PPARg agonist is inhibited by the MEK inhibitor PD98059, pertussis toxin, and antioxidant. Chemiluminescence study reveals that these three PPARg agonists are able to induce superoxide anion production, with efficacy order similar to their action on ERK phosphorylation. Consistent with this notion, we also show that O2- donor DMNQ causes ERK phosphorylation. We conclude that the PPARg agonists, 15d-PGJ2, ciglitazone and GW251929 can induce ERK activation through superoxide anion production and the Raf/MEK/ERK signaling pathway.
Part II:
Interleukin-4 (IL-4) is a multifunctional cytokine that controls inflammatory processes by suppressing the production of proinflammatory mediators at the transcriptional level, but the molecular mechanisms involved have not been elucidated. In mouse RAW 264.7 macrophages, consistent with the inhibition of LPS-induced NO and IL-6 production by Ro 31-8220 (a PKC inhibitor), PD 98059 (an MEK inhibitor), and SB 203580 (a p38 MAPK inhibitor), but not by wortmannin (a PI3K inhibitor), we show that IL-4 functions to block LPS-increased PKC, ERK, and p38 MAPK activities. All these protein kinases are known to play crucial roles in signal transduction pathways leading to iNOS and IL-6 gene transcription. PI3K activity, as assessed from its downstream target of Akt phosphorylation, is increased by LPS and IL-4 in an additive manner. Furthermore, IL-4 does not influence LPS-induced NF-kB activity as evidenced from its ineffectiveness on LPS induction of IKK activation and IkB degradation. Taken together, we conclude that uncoupling of the upstream signals for LPS induction of PKC, ERK, and p38 MAPK activation contributes to IL-4 inhibition of LPS-induced NO and IL-6 production.

第一部份1
英文摘要2
中文摘要3
緒論4
實驗材料及方法13
結果19
討論24
參考文獻38
第二部分49
英文摘要50
中文摘要51
緒論52
實驗材料與方法60
結果64
討論67
參考文獻76

Part I 參考文獻
Ashby, J., Brady, A., Elcombe, C.R., Elliot, B.M., Ishmael, J., Odum, J., Tugwood, J.D., Kettle, S. and Pruchase, I.F.H. (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. Exp. Toxicol. 13, S1-S117.
Avruch, J., Khokhlatchev, A.,.Kyriakis, J.M., Luo, Z., Tzivion, G.,. Vavvas, D., Zhang, X.F. (2001) Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinas cascade. Rec. Prog. Horm. Res. 56, 127-155.
Bailey, C.J. (2000) Potential new treatments for type 2 diabetes. Trend Pharmacol. Sci. 21, 259-265.
Bishop-Bailey, D. and Hla, T. (1999) Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy- D12,14-prostaglandin J2. J. Biol. Chem. 274, 17042.
Braissant, O., Foufelle, F., Scotto, C,. Dauca, M. and Wahli, W. (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-a, -b, and -g in the adult rat. Endocrinology. 137, 354-366.
Brown, K. K., Henke, B. R., Blandrard, S. G., Cobb, J. E., Mook, R., Kaldor, I., Kliewer, S.A., Lehmann, J.M., Lenhard, J.M., Harrington, W.W., Novak, P.J., et al. (1999) A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-g reverse diabetic phenotype of the Zucker Diabetic fatty rat. Diabetes 48, 1415-1424.
Castriro, A., Diaz-Guerra, M.J., Hortelano, S., Martin-Sanz, P. and Bosca, L. (2000) Inhibition of IkB kinase and IkB phosphorylation by 15-deoxy- D12,14-prostaglandin J2 in activated murine macrophages. Mol. Cell. Biol. 20, 1692.
Corton, J. C., Anderson, S. P. and Stauber, A. (2000) Central role of peroxisome proliferator-activated receptors in the action of peroxisome proliferators. Ann. Rev. Pharmacol. Toxicol. 40, 491-518.
Daum, G., Eisenmann Tappe, I., Fries, H.W., Troppmair, J. and Rapp, U.R. (1994) The ins and outs of Raf kinases.. Trends Biochem. Sci. 19, 474-480.
Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., and Wahli, W. (1996). The PPARg-leukotriene B4 pathway to inflammation control. Nature 384, 39-43.
Forman, B. M., Tontonoz, P., Chen, J., Brun, R.P., Spiegelman, B.M., Evans, R.M. (1995) 15-deoxy- D12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARg. Cell 83, 803-812.
Fukushima, M. (1990) Prostaglandin J2-anti-tumor and anti-viral activities and the mechanisms involved. Eicosanoids 3, 189-199.
Gao, Z., Chen, T., Weber, M. J. and Linden, J. (1999) A2B Adenosine and P2Y2 receptors stimulate mitogen-activated protein kinase in human embryonic kidney-293 Cells. J. Biol. Chem. 274, 5972-5980.
Grasl-Kraupp, B., Huber, W., Timmermann-Trosiener, I. and Schulte-Hermann, R. (1993) Peroxisomal enzyme induction uncoupled from enhanced DNA synthesis in putative preneoplastic liver foci of rats treated with a single dose of the peroxisome proliferator nafenopin. Carcinogenesis 14, 2435-2437.
Hagemann, C. and Rapp, U. R. (1999) Isotype-specific functions of Raf kinases. Exp. Cell Res. 253, 34-46.
Ho, K. J., Chen, P. Q., Chang, C. Y. and Lu, F. J. (2000) The oxidative metabolism of circulating phagocytes in ankylosing spondylitis: determination by whole blood chemiluminescence. Ann. Rheum. Dis. 59, 338-341.
Hortelano, S., Castrillo, A., Alvarez, A.M. and Bosca, L. (2000) Contribution of cyclopentenone prostaglandins to the resolution of inflammation through the potentiation of apoptosis in activated macrophages. J. Immunol. 165, 6525-6531.
Hu, E., Kim, J.B., Sarraf, P. and Spiegelman, B.M. (1996) Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science 274: 2100-2103.
Issemann, I. and Green, S. (1990). Activation of a member of the steroid receptor superfamily by peroxisome proliferators. Nature 347, 645-650.
Jiang, C., Ting, A. T. and Seed, B. (1998) PPAR-g agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82-86.
Kanoh, Y., Ishizuka, T., Morita, H., et al., (2000) Effect of pertussis toxin on insulin-induced signal transduction in rat adipocytes and soleus muscles. Cell. Signal. 12, 223-232.
Keller, H., Dreyer, C., Medin, J., Mahfoudi, A., Ozato, K., and Wahli, W. (1993) Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator activated receptor-retinoid X receptor heterodimers. Proc. Natl. Acad. Sci. USA 90, 2160-2164.
Kliewer, S. A., Lenhard, J. M., Willson, T. M., et al. (1995) A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor g promotes adipocyte differentiation. Cell 83, 813-819.
Kliewer, S. A., Umesono, k., Noonan, D. J., Heyman, R. A. and Evans, R. M. (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358, 771-774.
Krisans, S. K. (1992) The role of peroxisomes in cholesterol metabolism. Am. J. Respir. Cell Mol. Biol. 7, 358-364
Ledwith, B. J., Johnson, T. E., Wagner, L. K., Pauley, C. J., Manam, S., Galloway, S. M. and Nichols W. W. (1996) Growth regulation by peroxisome proliferators: opposing activities in early and late G1. Cancer Res. 56, 3257-64.
Lee SS. Pineau T. Drago J. Lee EJ. Owens JW. Kroetz DL. Fernandez-Salguero PM. Westphal H. Gonzalez FJ. (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell. Biol. 15, 3012-3022
Lehmann, J. M., Moore, L.B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M. and Kliewer, S. A. (1995) An antidiabetic is a high affinity ligand for peroxisome proliferator-activated receptor g (PPARg) J. Biol. Chem. 270, 12953-12956.
Lemberger, T., Desvergne, B., and Wahli, W. (1996). Peroxisome proliferator-activated receptors: A nuclear receptor signalling pathway in lipid physiology. Ann.. Rev. Cell Dev. Biol. 12, 335-363.
Lopez-Ilasaca M. Crespo P. Pellici PG. Gutkind JS. Wetzker R. (1997) Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma. Science. 275, 394-7
Mangelsdorf, D. J., and Evans, R. M. (1995). The RXR heterodimers and orphan receptors. Cell 83, 841-950.
Mangelus, M., Kroyter, A., Galron, R., Sokolovsky, M. (2001) Reactive oxygen species regulate signaling pathways induced by M1 muscarinic receptors in PC12M1 cells. J. Neurochem. 76, 1701-11
Mannaerts, G. P., and Van Veldhoven, P. P. (1993). Metabolic pathways in mammalian peroxisomers. Biochemie 75, 147-158.
Marais R. Light Y. Paterson HF. Marshall CJ. (1995) Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J. 14, 3136-45
Miwa, Y., Sasaguri, T., Inoue, H., Taba, Y., Ishida, A. and Abumiya, T. (2000) 15-Deoxy-D12,14-prostaglandin J2 induces G1 arrest and differentiation marker expression in vascular smooth muscle cells. Mol. Pharmacol. 58, 837-844.
Monick, M,M., Carter, A.B., Flaherty, D.M., Peterson, M.W., Hunninghake, G.W. (2000) Protein kinase C zeta plays a central role in activation of the p42/44 mitogen-activated protein kinase by endotoxin in alveolar macrophages. J Immunol. 165, 4632-9
Moody, D.E., Montgomery, K.A., Ashour, M.B., Hammock, B.D. (1991) Effects of environmentally encountered epoxides on mouse liver epoxide-metabolizing enzymes. Biochem. Pharmacol. 41,1625-37
Murphy, G. J., and Holder, J. C. (2000) PPARg agonists:therapeutic role in diabetes, inflammation and cancer. TiPS 21, 469-474.
Nakielny S. Campbell DG. Cohen P. (1992) MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction. FEBS Lett. 308, 183-9
Orbea, A., Beier, K., Volkl, A., Fahimi, H. D., and Cajaraville, M. P. (1998). Fish liver peroxisomes: Acell compartment involved in lipid metabolism and oxyradical homeostasis. J. Histochem. Cytochem. 46, A22.
Palmer, C. N. A., Hsu, M. H., Griffin, K. G., Raucy, J. L., Johnson, E. F. (1998) Peroxisome proliferator activated receptor-a expression in human liver. Mol. Pharmacol. 53, 14-22.
Pasceri, V., Wu, H. D., Willerson, J. T. and Yeh, E. T. H. (2000) Modulation of vascular inflammation in vitro and in vivo by perxisome proliferator activated receptor-r activators. Circulation 101, 235-238.
Pedersen, J. I. (1993) Peroxisomal oxidation of the steroid site chain in bile acid formation. Biochimie 75, 159-165.
Reginato, M. J., Krakow, S. L., Bailey, S. T. and Lazar, M. A. (1998) Prostaglandins promote and block adipogenesis through opposite effects on peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 273, 1855-1858.
Reuter, C.W.M., Morgan, M. A., and LotharBergmann. (2000) Targeting the Ras signaling pathway:a rational, mechanism-based treatment for hematologic malignancies? Blood 96, 1655-1669.
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J. and Glass, C. K. (2000) The peroxisome proliferator-activated receptor-g is a negative regulator of macrophage activation. Nature 391, 79-82.
Rokos, C.L. and Ledwith, B.J. (1997) Peroxisome proliferators activate extracellular signal-regulated kinases in immortalized mouse liver cells. J. Biol. Chem. 272, 13452-13457.
Rossi, A., Elia, G. and Santoro, M. (1996) 2-Cyclopenten-1-one, a new inducer of heat shock protein 70 with antiviral activity. J. Biol. Chem. 271, 32192-32196.
Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M. and Santoro, M.G. (2000) Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkB kinase. Nature 403, 103.
Sakatsume, M., Stancato, LF., David, M., Silvennoinen, O., Saharinen, P., Pierce, J., Larner, AC., Finbloom, DS. (1998) Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent. J. Biol. Chem. 273, 3021-3026
Saltiel, A. R. (2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104, 517-529.
Shalev A. Siegrist-Kaiser CA. Yen PM. Wahli W. Burger, AG. Chin WW. Meier CA. (1996) The peroxisome proliferator-activated receptor a is a phosphoprotein: regulation by insulin. Endocrinology. 137, 4499-502,
Singh, I. (1997). Biochemistry of peroxisomes in health and disease. Mol. Cel. Biochem. 167, 1-29.
Skolnik, EY., Lee CH., Batzer, A., et al., (1993) The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J. 12,1929-1936.
Smith, W. L., Marnett, L. J., DeWitt, D. L. (1991) Prostaglandin and thromboxane biosynthesis. Pharma. Ther. 49, 153-179.
Takeda, H., Matozaki, T., Takada, T., et al., (1999) PI 3-kinas g and protein kinas c-z mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor. EMBO J. 18, 386-395.
Terlecky, S. R., Wiemer, E. A., Nuttley, W. M.., Walton, P. W. and Subramani, S. (1996) Signals, receptors, and cytosolic factors involved in peroxisomal protein import. Ann. N. Y. Acad. Sci. 804, 11-20
Vaidya, S., Somers, E. P., Wright, S. D., Detmers, P. A. and Bansal, V. S. (1999) 15-Deoxy-D12,14-prostaglandin J2 inhibits the b2 intergrin-dependent oxidative burst: involvement of a mechanism distinct from peroxime proliferator-activated receptor g ligation. J. Immunol. 163, 6187-6192.
Van den Munckhof, R. J. M., Denyn, M., Tigchelaar-Gutter, W., Schipper, R. G., Verhofstaad, A. A. J., Van Noorden, C. J. M., and Frederiks, W. M. (1995a). In situ substrate specificity and ultrastructural localization of polyamine oxidase activity in unfixed rat tissues. J. Histochem. Cytochem. 43, 1155-1162.
Van den Munckhof, R. J. M., Vreeling- Sindelerova, H., Schellens, J. P. M., Van Noorden, C. J. F., and Freederiks, W. M. (1995b). Ultrastructural localization of xanthine oxidase activity in the digestive tract of the rat. Histochem. J. 27, 897-905
Wahli, W., Braissant, O. and Desvergne, B. (1995) Peroxisome proliferator-activated receptors:transcriptional regulators of adipogenesis, Lipid metabolism and more. Chem. Biol. 2, 261-266.
Weinberger, C. (1996). A model for farnesoid feedback control in the mevalonate patgway. Trends Endocrinol. Metab. 7, 1-6
Willson, TM., Lehmann, JM., Kliewer, SA. (1996) Discovery of ligands for the nuclear peroxisome proliferator-activated receptors. Ann. N. Y. Acad Sci. 804:276-283
Wright, H. M., Clish, C. B., Mikami, T., Hauser, S., Yanag, K., Hiramatsu, R., Serhan, C. N., Spiegelman, B. M. (2000) A synthetic antagonist for the peroxisome prpliferator activated receptor g inhibits adipocyte differentiation J. Biol. Chem. 275, 1873-1877.
Yu, K., Bayona, W., Kallen, C. B., Harding, H. P., Ravera, C. P., Mcmahon, G., Brown, M., Lazar, M. A. (1995) Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J. Biol. Chem. 270, 23975-23983.
Zhang, B., Berger, J., Zhou, G., Elbrecht, A., Biswas, S., White-Carrington, S., Szalkowski, D. and Moller, D.E. (1996) Insulin and mitogen-activated protein kinase-mediated phosphorylation and activation of peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 271, 31771-31774.
Zwacka, R. M., Reuier, A., Plaff, E., Moll, J., Gorgas, K., Karasawa, M., and Weiher, H. (1994) The glomerulosclerosis gene MPV17 encodes a peroxisomal protein producing reactive oxygen species. EMBO J. 13, 5129-5134.
Part II 參考文獻
Ajizian, S.J., English, B.K., Meak, E.A. (1999) Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J. Infection Dis. 179, 939-944.
Alaaeddine, N., Di Battista, J.A., Pelletier, J.P., Kiansa, K., Cloutier, J.M., Martel-Pelletier, J. (1999) Inhibition of tumor necrosis factor a-induced prostaglandin E2 production by the antiinflammatory cytokines interleukin-4, interleukin-10, and interleukin-13 in osteoarthritic synovial fibroblasts. Arthritis Rheum. 42, 710-718.
Baldwin, A.S. (1996) The NF-kB and IkB proteins: new discoveries and insights. Ann. Rev. Immunol. 14, 649-681.
Beutler,B. (2000) Tlr4: central component of the sole mammalian LPS sensor. Curr. Opin. in Immumol. 12, 20-26
Bogdan, C., Vodovotz, Y., Paik, J. Xie, Q., Nathan, C. (1994) Mechanism of suppression of NOS expression by IL-4 in primary mouse macrophages. J. Leukocyte Biol. 55, 227-233.
Chan, E.D., Riches, D.W. (1998) Potential role of the JNK/SAPK signal transduction pathway in the induction of iNOS by TNF-alpha. Biochem. Biophys. Res. Commun. 253, 790-796.
Chen, B.C., Chen, Y.H., Lin, W.W. (1999) Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages. Immunology. 97, 124-129.
Chen, B.C., Chou, C.F., Lin, W.W. (1998) Pyrimidinoceptor-mediated potentiation of inducible nitric-oxide synthase induction in J774 macrophages. J. Biol. Chem. 273, 29754-29763.
Chen, B.C., Lin, W.W. (1999) Potentiation of lipopolysaccharide-induced IL-6 release by uridine triphosphate in macrophages: cross-interaction with cyclooxygenase-2-dependent prostaglandin E2 production. J. Biomed. Sci. 6, 425-432.
Chen, Z., Parent, L., Maniatis, T. (1996) Site-specific phosphorylation of IkBa by a novel ubiquitin-dependent kinase activity. Cell 84, 853-862.
Dendorfer, U., Oettgen, P., Libermann, T.A. (1994) Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cAMP, and lipopolysaccharide. Mol. Cell. Biol. 14, 4443-4454.
Diaz-Guerra, M.J., Castrillo, A., Martin-Sanz, P., Bosca, L. (1999) Negative regulation by phosphatidylinositol 3-kinase of inducible nitric oxide synthase expression in macrophages. J. Immunol. 162, 6184-6190.
DiDonato, J.A., Hayakawa, M., Rothwarf, D.M., Zandi, E., Karin, M. (1997) A cytokine-responsive IkB kinase that activates the transcription factor NF-kB. Nature 388, 548-554.
Foey, A.D., Parry, S.L., Williams, L.M., Feldmann, M., Foxwell, B.M.J., Brennan, F.M. (1998) Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-a: role of the p38 and p42/44 mitogen-activated protein kinase. J. Immunol. 160, 920-928.
Fujihara, M., Connolly, N., Ito, N., Suauki, T. (1994) Properties of protein kinase C isoforms (bII, e and z) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production. J. Immunol. 152, 1898-1906.
Ghosh, G., Van Duyne, G., Ghosh, S., Sigler, P.B. (1995) Structure of NF-kB p50 homodimer bound to a kB site. Nature 373, 303-310.
Ghosh, S., May, M.J., Kopp, E.B. (1998) NF-kB and Rel proteins: evolutionarily conserved mediators of immune responses. Ann. Rev. Immunol. 16, 225-260.
Herlaar, E., Brown, Z. (1999) p38 MAPK signalling cascades in inflammatory disease. Mol. Med. Today 5, 439-447.
Huang, J.T., Welch, J.S., Ricote, M., Binder, C.J., Willson, T.M.., Kelly, C., Witztum, J.L., Funk, C.D., Conrad, D., Glass, C.K. (1999) Interleukin-4-dependent production of PPAR-g ligands in macrophages by 12/15-lipoxygenase. Nature 400, 378-382.
Ihle, J.N., Kerr, I.M. (1995) Jaks and Stats in signalling by the cytokine receptor superfamily. Trends Genet. 11, 69-74.
Ikizawa, K., Kajiwara, K., Basaki, Y., Koshio, T., Yanagihara, Y. (1996) Evidence for a role of phosphatidylinositol 3-kinase in IL-4-induced germline C epsilon transcription. Cell. Immunol . 170, 134-140.
James, E. and Darnell J. (1997) STATs and gene regulation. Science 277, 1630-1635
Jungi, T.W., Brcic, M., Sager, H., Dobbelaere, D.A.E., Furger, A., Roditi, I. (1997) Antagonistic effects of IL-4 and interferon-gamma (IFN-g) on inducible nitric oxide synthase expression in bovine macrophages exposed to Gram-positive bacteria. Clin. Exp. Immunol. 109, 431-438.
Kaliman, P., Canicio, J., Testar, X., Palacin, M., Zorzano, A. (1999) Insulin-like growth factor-II, phosphatidylinositol 3-kinase, nuclear factor-kB and inducible nitric-oxide synthase define a common myogenic signaling pathway. J. Biol. Chem. 274, 17437-17444.
Karin, M. (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270, 16483-16486.
Larsen, C.M., Wadt, K.A.W., Juhl, L.F., Andersen, H.U., Karlsen, A.E., Su, M.S.S., et al. (1998) Interleukin-1b-induced rat pancreatic islet nitric oxide synthesis requires both the p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases. J. Biol. Chem. 273, 15294-15300.
Lee, J.C., Laydon, J.T., Mcdonnell, P.C., Gallagher, T.F., Kumar, S., Green, D., et al. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372, 739-746.
Manna, S.K., Aggarwal, B.B. (1998) Interleukin-4 down-regulates both forms of tumor necrosis factor receptor and receptor-mediated apoptosis, NF-kB, AP-1, and c-Jun N-terminal kinase. J. Biol. Chem. 273, 33333-33341.
Nelms, K., Keegan, A.D., Zamorano, J., Ryan, J.J., Paul, W.E. (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu. Rev. Immunol. 17, 701-738.
Ozes, O.N., Mayo, L.D., Gustin, J.A., Pfeffer, S.R., Pfeffer, L.M., Donner, D.B. (1999) NF-kB activation by tumor necrosis factor requires the Akt serine-threonine kinase. Nature 401, 82-85.
Paludan, S.R., Ellermann-Eriksen, S., Lovmand, J., Mogensen, S.C. (1999) Interleukin-4-mediated inhibition of nitric oxide production in interferon-g-treated and virus-infected macrophages. Scand. J. Immunol. 49, 169-176.
Pan, Z.K., Christiansen, S.C., Ptasznik, A., Zuraw, B.L. (1999) Requirement of phosphatidylinositol 3-kinase activity for bradykinin stimulation of NF-kB activation in cultured human epithelial cells. J. Biol. Chem. 274, 9918-9922.
Reilly, C. M., Oates, J.C., Suduan, J., Crosby, M.B., Halushka, P.V., Gilkeson, G.S. (2001) Prostaglandun J2 inhibition of mesangial cell iNOS expression. Clin Immunol 98, 337-345
Schindler, C., Darnell, J.E. (1995) Transcriptional responses to polypeptide ligands: the Jak-Stat pathway. Annu. Rev. Biochem. 64, 621-651.
Schottelius, A.J.G., Mayo, M.W., Sartor, R.B., Baldwin, A.S. Jr. (1999) Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J. Biol. Chem. 274, 31868-31874.
Szabo, C., Zingarelli, B., O’Connor, M., Salzman, A.L. (1996) DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc. Natl. Acad. Sci. USA 93, 1753-1758.
Takeda, K., Kamanaka, M., Tanaka, T., Kishimoto, T., Akira, S. (1996) Impaired IL-13 mediated function of macrophages in STAT-6 deficient mice. J. Immunol. 157, 3220-3222.
Takeda, K., Tanaka, T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S., et al. (1996) Essential role of Stat6 in IL-4 signalling. Nature 380, 627-630.
Te Velde, A.A., Huijbens, R.J., Heije, K., De Vries, J.E., Figdor, C.G. (1990) Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor-alpha, and IL-6 by human monocytes. Blood 76, 1392-1397.
Vanden Berghe, W., Plaisance, S., Boone, E., De Bosscher, K., Schmitz, M.L., Fiers, W., Haegeman, G. (1998) p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kB p65 transactivation mediated by tumor necrosis factor. J. Biol. Chem. 273, 3285-3290.
Wang, Y., Wu, T. R., Cai, S., Welte, T., and Chin, Y. E. (2000) Stat1 as a componment of Tumor Necrosis Factor a receptor 1- TRADD signaling complex to inhibit NF-kB activation. Mol. Cell. Biol. 20 ,4505-4512
Whitmarsh, A.J., Shore, P., Sharrocks, A.D., Davis, R.J. (1995) Integration of MAP kinase signal transduction pathways at the serum response element. Science 269, 403-407.
Xie, Q.W., Whisnant, R., Nathan, C. (1993) Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon g and bacterial lipopolysaccharide. J. Exp. Med. 177, 1779-1784.
Zandi, E., Rothwarf, D.M., Delhase, M., Hayakawa, M., Karin, M. (1997) The IkB kinase complex (IKK) contains two kinase subunits, IKKa and IKKb, necessary for IkB phosphorylation and NF-kB activation. Cell 91, 243-252.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊