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.
