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KMID : 1034820110070010039
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Molecular & Cellular Toxicology
2011 Volume.7 No. 1 p.39 ~ p.39
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Suppression of cyclooxygenase-2 expression induced by Toll-like receptor 2 or 4 agonists by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate
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Lee A-Neum
Park Se-Jeong
Koh Kwang-Oh
Kim Dae-Young
Youn Hyung-Sun
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Abstract
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Inflammation can be initiated by invading microbial pathogens. Toll-like receptors (TLRs) recognize molecular structures derived from microbial pathogens and regulate the activation of innate immunity. TLR signaling pathways trigger the activation of nuclear factor-κB(NF-κB) transcription factor, leading to the induction of inflammatory gene products such as cyclooxygenase-2. Here, we present biochemical evidence that the fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate (IPOP), previously synthesized in our laboratory inhibits NF-κB activation induced by TLR agonists and overexpression of two downstream signaling components of TLRs. IPOP also inhibits TLR agonist-induced expression of cyclooxygenase-2. Our results suggest that IPOP can modulate TLR-mediated inflammatory responses and, potentially, the risk of many chronic inflammatory diseases.
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KEYWORD
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Toll-like receptor, Lipopolysaccharide, Cyclooxygenase-2, Nuclear factor-κB, Fumaryl pyrrolidinone
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