https://scholars.lib.ntu.edu.tw/handle/123456789/564605
標題: | Involvement of 15-lipoxygenase in the inflammatory arthritis | 作者: | Wu M.-Y. Lin T.-H. Chiu Y.-C. Liou H.-C. RONG-SEN YANG WEN-MEI FU |
公開日期: | 2012 | 卷: | 113 | 期: | 7 | 起(迄)頁: | 2279-2289 | 來源出版物: | Journal of Cellular Biochemistry | 摘要: | 15-Lipoxygenase (15-LOX) is involved in many pathological processes. The aim of this study is to examine the role of 15-LOX in the matrix metalloproteinase (MMP) expression and inflammatory arthritis. It was found that treatment of 15-LOX downstream product of 15-(S)-HETE (15-S- hydroxyeicosatetraenoic acid) increased the mRNA and protein levels of MMP-2 in rheumatoid arthritis synovial fibroblast (RASF) derived from rheumatoid arthritis patients. The enhancement effect of 15-(S)-HETE was antagonized by the addition of LY294002 (PI3K inhibitor) and PDTC (NF-κB inhibitor). Treatment of 15-(S)-HETE increased the phosphorylation of AKT, nuclear translocation of p65 and the breakdown of IIα. TNF-α and IL-1β are the key cytokines involved in arthritis and also increase the activity of MMP-2 in RASF, which was antagonized by pretreatment with 15-LOX inhibitor PD146176 or knockdown of 15-LOX. It was also found that these two cytokines increased the expression of 15-LOX in RASF. Treatment of glucocorticoid but not NSAIDs inhibited 15-(S)-HETE-induced expression of MMP-2. In comparison with wild-type mice, adjuvant-induced arthritis and MMP-2 expression in synovial membrane were markedly inhibited in 15-LOX knockout (KO) mice. These results indicate that 15-LOX plays an important role in the disease progression of arthritis and may be involved in the inflammatory action induced by TNF-α and IL-1β. 15-LOX is thus a good target for developing drugs in the treatment of inflammatory arthritis. ? 2012 Wiley Periodicals, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564605 | ISSN: | 7302312 | DOI: | 10.1002/jcb.24098 | SDG/關鍵字: | 15 hydroxyicosatetraenoic acid; 2 morpholino 8 phenylchromone; arachidonate 15 lipoxygenase; gelatinase A; glucocorticoid; I kappa B alpha; immunoglobulin enhancer binding protein; interleukin 1beta; matrix metalloproteinase; protein kinase B; pyrrolidine dithiocarbamate; synaptotagmin I; tumor necrosis factor alpha; animal tissue; article; fibroblast; human; human cell; mouse; nonhuman; priority journal; protein expression; protein phosphorylation; rheumatoid arthritis; rheumatoid arthritis synovial fibroblast; synovium; wild type; Animals; Arachidonate 15-Lipoxygenase; Arthritis, Experimental; Arthritis, Rheumatoid; Cells, Cultured; Chromones; Eicosapentaenoic Acid; Fibroblasts; Fluorenes; Humans; I-kappa B Kinase; Interleukin-1beta; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Phosphatidylinositol 3-Kinases; Phosphorylation; Proline; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Messenger; RNA, Small Interfering; Synovial Membrane; Thiocarbamates; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Mus |
顯示於: | 藥理學科所 |
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