Document Detail

Interferon-beta induces metalloproteinase mRNA expression in human fibroblasts. Role of activator protein-1.
MedLine Citation:
PMID:  8063804     Owner:  NLM     Status:  MEDLINE    
Matrix metalloproteinases are secreted enzymes important in inflammation and tumor invasion. Earlier, we demonstrated that in normal human FS-4 fibroblasts, collagenase and stromelysin mRNA levels are increased not only after treatment with known matrix metalloproteinase inducers such as tumor necrosis factor (TNF), interleukin-1, and 12-O-tetradecanoylphorbol-13-acetate, but also with interferon-beta (IFN-beta). In this study, we compared the regulation of these matrix metalloproteinase genes by TNF and IFN-beta. We show that both TNF and IFN-beta increase steady-state levels of collagenase and stromelysin mRNAs with similar slow kinetics. The glucocorticoid dexamethasone blocked matrix metalloproteinase induction by both cytokines. The protein synthesis inhibitor cycloheximide inhibited collagenase mRNA induction by TNF or IFN-beta, suggesting that induction by both agents is indirect. Consistent with these observations, both TNF and IFN-beta increased c-fos and c-jun mRNA levels. Furthermore, treatment with TNF or IFN-beta increased the transcriptional activity of activator protein-1-responsive chloramphenicol acetyltransferase reporter gene constructs, including a native collagenase promoter-driven chloramphenicol acetyltransferase construct. These findings show that regulation of matrix metalloproteinase gene expression by both TNF and IFN-beta involves the transcription factor activator protein-1 and demonstrate a novel indirect mechanism of type I IFN-induced gene expression.
P J Sciavolino; T H Lee; J Vilcek
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-22     Completed Date:  1994-09-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21627-34     Citation Subset:  IM    
Department of Microbiology, New York University Medical Center, New York 10016.
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MeSH Terms
Base Sequence
Cells, Cultured
Collagenases / biosynthesis,  genetics
Cytokines / pharmacology
Dexamethasone / pharmacology
Enzyme Induction / drug effects
Extracellular Matrix / enzymology*
Fibroblasts / metabolism
Genes, Reporter
Interferon-beta / pharmacology*
Matrix Metalloproteinase 3
Metalloendopeptidases / biosynthesis*,  genetics
Molecular Sequence Data
Protein Binding / drug effects
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism*
RNA, Messenger / biosynthesis
Tetradecanoylphorbol Acetate / pharmacology
Transcription, Genetic*
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
Reg. No./Substance:
0/Cytokines; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 16561-29-8/Tetradecanoylphorbol Acetate; 50-02-2/Dexamethasone; 77238-31-4/Interferon-beta; EC 3.4.24.-/Collagenases; EC 3.4.24.-/Metalloendopeptidases; EC Metalloproteinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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