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Accession number;02A0146454
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| Title;The Mechanism regarding Prostaglandin E2 Production in Activated Macrophages: Arginine Metabolites in NO-Independent Pathway. |
| Author;
OTSUKA MARI
(Tohodai I Bunshiseibutsugakukenkyushitsu)
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Journal Title;Journal of the Medical Society of Toho University
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Journal Code:G0654A
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ISSN:0040-8670
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VOL.48;NO.6;PAGE.402-411(2001)
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| Figure&Table&Reference;FIG.6, TBL.1, REF.28 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Activated macrophages (M.PHI.) play an important role in inflammatory response by releasing various mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2). To clarify the mechanism by which PGE2 production is regulated by activated M.PHI., the effect of arginine (Arg) metabolites including NO on PGE2 production was studied in the murine M.PHI.-like cell line RAW 264.7. The amount of PGE2 released by RAW 264.7 cells co-stimulated by interferon-.GAMMA. and bacterial lipopolysaccharide in Arg-depleted medium was quadruple that obtained in Arg-supplemented medium. An increase in PGE2 production -a half that in Arg-depleted medium was also observed, when cells were treated with an inducible NO synthase inhibitor in Arg-supplemented medium. These results indicate that PGE2 production in activated M.PHI. is regulated via NO-dependent and -independent pathways. To identify the Arg metabolites participating in the NO-independent regulatory pathway, the effects of various metabolites were examined next. Citrulline and urea were found to suppress PGE2 production. Further, an arginase inhibitor increased PGE2 production, suggesting that urea is involved in PGE2 synthesis. However, urea and citrulline did not suppress recombinant cyclooxygenase-2 (COX-2), indicating that these Arg metabolites may regulate COX-2 gene expression or one of the PGE2 synthetic enzymes other than COX-2. These results suggest that PGE2 production in activated M.PHI. is regulated by Arg metabolites including NO, urea and citrulline. Microenvironmental Arg status may be critical in determining which mediators are predominantly released in an inflammatory response. (author abst.) |
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