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.
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.
Yun
Sae-mi
SM
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
Kang
Seung Hee
SH
Lee
A-neum
AN
Park
Se-jeong
SJ
Kim
Dae Young
DY
Youn
Hyung-sun
HS
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*
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