Retinoid acid inhibits IL-1-induced iNOS, COX-2 and chemokine production in human chondrocytes

Li Feng Hung, Jenn Haung Lai, Leou Chyr Lin, Shyu Jye Wang, Tsung Yun Hou, Deh Ming Chang, Chun Chin T. Liang, Ling Jun Ho

研究成果: 雜誌貢獻文章同行評審

19 引文 斯高帕斯(Scopus)

摘要

This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E2. In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10-1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA.
原文英語
頁(從 - 到)675-693
頁數19
期刊Immunological Investigations
37
發行號7
DOIs
出版狀態已發佈 - 十月 1 2008
對外發佈

ASJC Scopus subject areas

  • 免疫學

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