Prostaglandin ei inhibits collagenase gene expression in rabbit synoviocytes and human fibroblasts

Roberto Salvatori, Peter T. Guidon, Bruce E. Rapuano, Richard S. Bockman

Research output: Contribution to journalArticlepeer-review

Abstract

Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can be mediated by proteolytic enzymes, such as the metalloproteinase collagenase, the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene expression can be stimulated by the phorbol ester tumor promoter 12-0-tetradecanoyl-phorbol-13-ace- tate. We have investigated the effect of prostaglandin E1 (PGEi) on 12-0-tetradecanoyl-phorbol-13-acetate-stimulated collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not PGE2 or PGF was able to selectively reduce collagenase mRNA levels in a dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP, while PGE2 and PGF, had little or no effect on cAMP production in the HIG-82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX), mimicked the effect of PGEi on collagenase mRNA levels. PGE1; forskolin, and IBMX also decreased collagenase mRNA levels in human skin fibroblasts, demonstrating that this observation was not unique to the HIG-82 cell line. Transient transfection experiments carried out in HIG-82 cells using a 1.2-kilobase portion of the 5'-flanking region of the human collagenase gene linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and IBMX exert their inhibitory effect on the promoter region of the collagenase gene.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalEndocrinology
Volume131
Issue number1
DOIs
StatePublished - Jul 1992
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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