title: Effect of retinoids on LPS-induced COX-2 expression and COX-2 associated PGE(2) release from mouse peritoneal macrophages and TNF-alpha release from rat peripheral blood mononuclear cells.
abstract: Anti-inflammatory activity of retinoids has been demonstrated earlier, but their mechanism is poorly understood. In this study, we examined the effects of retinoids on lipopolysaccharide (LPS)-induced prostaglandin (PG) E(2) production, an indicator of cyclooxygenase (COX) activity, and COX-2 protein expression in mouse peritoneal macrophages, and tumor necrosis factor (TNF)-alpha release in rat peripheral blood mononuclear cell (PBMC) to elucidate their possible mechanism for anti-inflammation. All-trans retinoic acid (t-RA) and all-trans retinol significantly inhibited a LPS-induced PGE(2) production as assessed by enzyme-linked immunosorbant assay (ELISA) and COX-2 protein expression as assessed by Western blot assay in mouse peritoneal macrophages, after knocking out the COX-1 activity by aspirin. All-trans retinoic acid, but not all-trans retinol, inhibited LPS-induced TNF-alpha release as assessed by ELISA in rat PBMC. These findings suggest that the modulation of COX-2 and TNF-alpha release could be one of the possible pathways by which retinoids function as anti-inflammatory agents.
authors.affiliation: Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Bae-Hwan
authors.initials: BH
authors.lastname: Kim
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Yong-Soon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D007527:Isoenzymes / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008070:Lipopolysaccharides; D012176:Retinoids; D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; D014212:Tretinoin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone