Back to Search
Start Over
Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2005 Jul 15; Vol. 70 (2), pp. 200-8. - Publication Year :
- 2005
-
Abstract
- The development of osteoarthritis (OA) has recently been implicated as a result of immune-mediated damage of chondrocytes and their supporting matrixes. Pro-inflammatory cytokines like interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) play pivotal roles in immunopathogenesis of OA. Because vitamins preserving anti-oxidative effects are suggested to provide protection in OA patients from joint damage, in the present study, we examined the effects and mechanisms of all-trans retinoic acid (t-RA) in suppressing pro-inflammatory cytokine-induced matrix metalloproteinases (MMPs) production in human chondrocytes. Chondrocytes were prepared from cartilage specimens of OA patients receiving total hip or total knee replacement. The protein concentration was measured by ELISA, the mRNA expression by reverse transcriptase-polymerase chain reaction, the protein expression by Western blotting, the transcription factor DNA-binding activity by electrophoretic mobility shift assay and the protein kinase activity by kinase assay. We showed that both MMP-1 and MMP-13 mRNA expression, protein production and enzyme activity induced by either IL-1 or TNF-alpha were suppressed by t-RA or different retinoid derivatives. The molecular investigation revealed that the t-RA-mediated suppression was likely through blocking p38 kinase and c-Jun N-terminal kinase-activator protein-1 signaling pathways. In contrast, t-RA had no effect on extracellular signal-regulated kinase activity, nuclear factor (kappa)B (NF-(kappa)B) DNA-binding activity and I(kappa)B(alpha) degradation. Furthermore, we showed that t-RA could reduce IL-1-induced TNF-alpha production in chondrocytes. Our results suggest that vitamin A may protect OA patients from pro-inflammatory cytokine-mediated damage of chondrocytes and their supporting matrixes.
- Subjects :
- Chondrocytes enzymology
Chondrocytes physiology
Cytokines pharmacology
Down-Regulation physiology
Humans
Inflammation Mediators antagonists & inhibitors
Inflammation Mediators pharmacology
Matrix Metalloproteinases biosynthesis
Mitogen-Activated Protein Kinase 8 biosynthesis
Protease Inhibitors pharmacology
Signal Transduction physiology
Transcription Factor AP-1 physiology
Chondrocytes drug effects
Cytokines antagonists & inhibitors
Down-Regulation drug effects
Matrix Metalloproteinase Inhibitors
Mitogen-Activated Protein Kinase 8 antagonists & inhibitors
Signal Transduction drug effects
Transcription Factor AP-1 antagonists & inhibitors
Tretinoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15946654
- Full Text :
- https://doi.org/10.1016/j.bcp.2005.04.039