Document Detail


Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2.
MedLine Citation:
PMID:  12445497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study was designed to investigate the effect of IL-1alpha-induced up-regulation of cyclooxygenase-2 (COX-2) on prostaglandin E(2) (PGE(2)) secretion and the subsequent phenotypic effects of PGE(2) on epithelial cells. The effect of IL-1alpha on COX-2 expression was investigated in the T24 bladder epithelial cell line following treatment with 0, 0.05, 0.5, 1 or 10 ng/ml IL-1alpha for 1, 2, 4 or 6 h. Quantitative PCR confirmed up-regulation of expression of COX-2 with maximal expression observed following treatment with 0.5 ng/ml IL-1alpha for 1 h. Co-treatment of the cells with 0.5 ng/ml IL-1alpha in the presence or absence of 100 ng/ml IL-1 receptor antagonist (RA) abolished the up-regulation in COX-2 expression confirming that the effect of IL-1alpha is mediated via its membrane-bound receptors. Treatment with 0.5 ng/ml IL-1alpha resulted in a time-dependent increase in PGE(2) secretion with maximal secretion detected at 24 and 48 h after stimulation with IL-1alpha. Co-treatment of the cells with IL-1alpha and IL-1RA or the COX-2 enzyme inhibitor NS398 abolished the IL-1alpha mediated secretion of PGE(2). Treatment of T24 cells with 100 nM PGE(2) resulted in a significant elevation in cAMP generation confirming the expression of functional PGE(2) receptors. Finally, the effect of exogenous treatment with PGE(2) on apoptosis of T24 cells was assessed using cell death detection ELISA. T24 cells were treated with camptothecin to induce apoptosis in the presence or absence of 50 or 100 nM PGE(2) or 10 microM forskolin. Treatment of T24 cells with increasing doses of camptothecin alone resulted in a significant increase in the induction of apoptosis (P<0.01). However, co-treatment of the cells with 50 or 100 nM PGE(2) or 10 microM forskolin resulted in the inhibition of induction of the apoptotic pathway by camptothecin. These data demonstrate that PGE(2) inhibits apoptosis of epithelial cells possibly via cAMP-dependent pathway.
Authors:
H N Jabbour; R W Kelly; S C Boddy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  67     ISSN:  0952-3278     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-26     Completed Date:  2003-12-12     Revised Date:  2010-09-20    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  357-63     Citation Subset:  IM    
Affiliation:
Human Reproductive Sciences, Centre for Reproductive Biology, The University of Edinburg Academic Centre, 49 Little France Crescent, UK. h.jabbour@hrsu.mrc.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Autocrine Communication*
Camptothecin / pharmacology
Cell Line
Cyclooxygenase 2
Dinoprostone / metabolism*,  secretion
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / cytology*,  drug effects*,  enzymology,  metabolism
Gene Expression Regulation, Enzymologic / drug effects
Interleukin-1 / pharmacology
Isoenzymes / antagonists & inhibitors,  metabolism
Paracrine Communication*
Polymerase Chain Reaction
Prostaglandin-Endoperoxide Synthases / metabolism
Ribonucleases
Grant Support
ID/Acronym/Agency:
U.1276.00.004.00002.01/2(61014)//Medical Research Council
Chemical
Reg. No./Substance:
0/Interleukin-1; 0/Isoenzymes; 363-24-6/Dinoprostone; 7689-03-4/Camptothecin; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 3.1.-/Ribonucleases

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


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