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Retinoid Acid Inhibits IL-1-Induced iNOS, COX-2 and Chemokine Production in Human Chondrocytes.
- Source :
- Immunological Investigations; Oct2008, Vol. 37 Issue 7, p675-693, 19p, 1 Black and White Photograph, 7 Graphs
- Publication Year :
- 2008
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- TRETINOIN
NUCLEIC acids
CYTOKINES
CELLULAR immunity
CARTILAGE cells
Subjects
Details
- Language :
- English
- ISSN :
- 08820139
- Volume :
- 37
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Immunological Investigations
- Publication Type :
- Academic Journal
- Accession number :
- 34506958
- Full Text :
- https://doi.org/10.1080/08820130802307237