| Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2. | |
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MedLine Citation:
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PMID: 12445497 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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H N Jabbour; R W Kelly; S C Boddy |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 2002-11-26 Completed Date: 2003-12-12 Revised Date: 2010-09-20 |
Medline Journal Info:
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Nlm Unique ID: 8802730 Medline TA: Prostaglandins Leukot Essent Fatty Acids Country: Scotland |
Other Details:
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Languages: eng Pagination: 357-63 Citation Subset: IM |
Affiliation:
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Human Reproductive Sciences, Centre for Reproductive Biology, The University of Edinburg Academic Centre, 49 Little France Crescent, UK. h.jabbour@hrsu.mrc.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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:
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U.1276.00.004.00002.01/2(61014)//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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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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