Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand Objective To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP‐1) and MMP‐13 induced by proinflammatory cytokines in a chondrocyte model. Methods SW‐1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin‐1β (IL‐1β)–stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively. Results LG268 treatment specifically antagonized the IL‐1β–mediated induction of MMP‐1 and MMP‐13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP‐1 and MMP‐13 transcription. LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL‐1β–treated SW‐1353 cells. The inhibitory effect of LG268 on MMP‐1 and MMP‐13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP‐1 and MMP‐13 promoters that contain binding sites for activator protein 1 transcription factors. Conclusion These data indicate that LG268 treatment selectively inhibits inflammatory cytokine–induced production of MMP‐1 and MMP‐13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine–stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arthritis & Rheumatism Wiley

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Download PDF
13 pages

Loading next page...
 
/lp/wiley/regulation-of-matrix-metalloproteinase-gene-expression-by-a-retinoid-x-0ifiHCGPF5

References (51)

Publisher
Wiley
Copyright
Copyright © 2007 by the American College of Rheumatology
ISSN
0004-3591
eISSN
1529-0131
DOI
10.1002/art.22417
pmid
17328062
Publisher site
See Article on Publisher Site

Abstract

Objective To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP‐1) and MMP‐13 induced by proinflammatory cytokines in a chondrocyte model. Methods SW‐1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin‐1β (IL‐1β)–stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively. Results LG268 treatment specifically antagonized the IL‐1β–mediated induction of MMP‐1 and MMP‐13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP‐1 and MMP‐13 transcription. LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL‐1β–treated SW‐1353 cells. The inhibitory effect of LG268 on MMP‐1 and MMP‐13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP‐1 and MMP‐13 promoters that contain binding sites for activator protein 1 transcription factors. Conclusion These data indicate that LG268 treatment selectively inhibits inflammatory cytokine–induced production of MMP‐1 and MMP‐13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine–stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides.

Journal

Arthritis & Rheumatism – Wiley

Published: Mar 1, 2007

There are no references for this article.