title: Suppression of Toll-like receptor 2 or 4 agonist-induced cyclooxygenase-2 expression by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester.
abstract: Toll-like receptors (TLRs) recognize molecular structures derived from microbes including bacteria, viruses, yeast, and fungi, and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of nuclear factor-kappaB (NF-kappaB) transcription factor leading to the induction of inflammatory gene products including cytokines and cyclooxygenase-2 (COX-2). In the present report, we demonstrate biochemical evidence that the fumaryl oxazolidinone derivative 4-Oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester (OSL07), which was previously synthesized in our laboratory, inhibits the NF-kappaB activation induced by TLR agonists and overexpression of downstream signaling components of TLRs, MyD88 and IKKbeta. OSL07 also inhibits TLR agonist-induced COX-2 expression. These results indicate that the anti-inflammatory effects of OSL07 are caused by the modulation of the immune responses regulated by TLR signaling pathways.
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Sae-mi
authors.initials: SM
authors.lastname: Yun
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kang
authors.forename: A-neum
authors.initials: AN
authors.lastname: Lee
authors.forename: Se-jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyung-sun
authors.initials: HS
authors.lastname: Youn
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics; D005650:Fumarates / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects; D023303:Oxazolidinones / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: C548711:4-oxo-4-(2-oxooxazolidin-3-yl)but-2-enoic acid ethyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005650:Fumarates; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D023303:Oxazolidinones; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase