Document Detail

Posttranscriptional effect of insulin-like growth factor-I on interleukin-1beta-induced type II-secreted phospholipase A2 gene expression in rabbit articular chondrocytes.
MedLine Citation:
PMID:  9109430     Owner:  NLM     Status:  MEDLINE    
Large amounts of type II-secreted phospholipase A2 (type II sPLA2) are secreted into inflammatory synovial fluid and they are believed to induce the synthesis of lipid mediators by articular chondrocytes. Preliminary experiments showed that insulin-like growth factor-I, which counteracts cartilage degradation in arthritis, inhibits interleukin-1beta-induced type II sPLA2 gene expression in rabbit articular chondrocytes (Berenbaum, F., G. Thomas, S. Poiraudeau, G. Bereziat, M.T. Corvol, and J. Masliah. 1994. FEBS Lett. 340: 51-55). The present study showed that IL-1beta induced the sustained synthesis of prostaglandin E2 and a parallel increase in type II sPLA2 gene expression (assessed by enzymatic activity and Northern blot analysis), but no increase in cytosolic PLA2 gene expression (assessed by Northern and Western blot analysis) or cytosolic PLA2 activity in rabbit articular chondrocytes. IGF-I inhibited both IL-1beta-stimulated PGE2 synthesis and type II sPLA2 gene expression, but had no effect on cytosolic PLA2 gene expression. Nuclear run-on experiments revealed that IL-1beta stimulated the transcription rate of type II sPLA2 gene, giving rise to long-lived mRNA in cells treated with actinomycin D. IGF-I did not affect transcription rate, suggesting that it acts as a post-transcriptional step. Sucrose density gradient analysis of the translation step showed no effect of IGF-I on the entry of type II sPLA2 mRNA into the polysomal pool or on its distribution into the various polysomal complexes, suggesting that IGF-I does not act on the translation of the mRNA. Lastly, IGF-I strongly decreased the half-life of IL-1beta-induced type II sPLA2 mRNA (from 92 to 12 h), suggesting that IGF-I destabilizes mRNA. These data demonstrate that IL-1beta stimulates the transcription rate of the type II sPLA2 gene and gives rise to a very stable mRNA. In contrast, IGF-I decreases the half-life of the type II sPLA2 message.
C Jacques; G Béréziat; L Humbert; J L Olivier; M T Corvol; J Masliah; F Berenbaum
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  99     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-09     Completed Date:  1997-05-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1864-72     Citation Subset:  AIM; IM    
Biochemistry and Molecular Biology Laboratory, Faculty of Medicine of St. Antoine, University Pierre and Marie Curie, Paris, France.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Cartilage, Articular / cytology,  drug effects*,  metabolism*
Cells, Cultured
DNA, Complementary / genetics
Dinoprostone / biosynthesis
Gene Expression Regulation, Enzymologic / drug effects
Insulin-Like Growth Factor I / pharmacology*
Interleukin-1 / pharmacology*
Molecular Sequence Data
Phospholipases A / classification,  genetics*,  metabolism
Phospholipases A2
RNA, Messenger / genetics,  metabolism
Recombinant Proteins / pharmacology
Ribosomes / drug effects,  metabolism
Sequence Homology, Amino Acid
Reg. No./Substance:
0/DNA, Complementary; 0/Interleukin-1; 0/RNA, Messenger; 0/Recombinant Proteins; 363-24-6/Dinoprostone; 67763-96-6/Insulin-Like Growth Factor I; EC 3.1.1.-/Phospholipases A; EC A2

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

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