Document Detail

Uncoordinate regulation of collagenase, stromelysin, and tissue inhibitor of metalloproteinases genes by prostaglandin E2: selective enhancement of collagenase gene expression in human dermal fibroblasts in culture.
MedLine Citation:
PMID:  8014195     Owner:  NLM     Status:  MEDLINE    
The degradative effects of interleukin-1 (IL-1) on the extracellular matrix of connective tissue are mediated primarily by metalloproteinases and prostaglandins. Clinical observations suggest that these effects can be prevented, to some extent, by the use of non-steroidal anti-inflammatory drugs. We have examined the role of prostaglandin E2 (PGE2) in IL-1-induced gene expression by human skin fibroblasts in culture. Incubation of confluent fibroblast cultures with varying concentrations (0.01-1.0 microgram/ml) of PGE2 led to a dose-dependent elevation of collagenase mRNA steady-state levels, the promoter activity, and the secretion of the protein, whereas relatively little effect was observed on stromelysin and TIMP gene expression. Exogenous PGE2 had no additive or synergistic effect with IL-1 on collagenase gene expression. Furthermore, commonly used non-steroidal anti-inflammatory drugs (indomethacin, acetyl salicylic acid and ibuprofen), at doses which block prostaglandin synthesis in cultured fibroblasts, failed to counteract IL-1-induced collagenase and stromelysin gene expression, nor did they affect TIMP expression. Although the effects of PGE2 did not potentiate those of IL-1 on collagenase gene expression in vitro, one could speculate that massive production of PGE2 by connective tissue cells in vivo in response to inflammatory mediators such as IL-1 or tumor necrosis factor-alpha, could lead to sustained expression of collagenase in connective tissue cells after clearance of the growth factors.
A Mauviel; C Halcin; P Vasiloudes; W C Parks; M Kurkinen; J Uitto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  54     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-07-26     Completed Date:  1994-07-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  465-72     Citation Subset:  IM    
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
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MeSH Terms
Cells, Cultured
Collagenases / genetics*,  secretion
Dinoprostone / pharmacology*
Fibroblasts / metabolism*
Gene Expression Regulation / drug effects*
Glycoproteins / genetics*
Interleukin-1 / pharmacology
Matrix Metalloproteinase 3
Metalloendopeptidases / genetics*
RNA, Messenger / metabolism
Tissue Inhibitor of Metalloproteinases
Transcription, Genetic / drug effects
Grant Support
Reg. No./Substance:
0/Glycoproteins; 0/Interleukin-1; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinases; 363-24-6/Dinoprostone; EC 3.4.24.-/Collagenases; EC 3.4.24.-/Metalloendopeptidases; EC Metalloproteinase 3

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