title: Suppression of the TRIF-dependent signaling pathway of toll-like receptors by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate.
abstract: Toll-like receptors (TLRs) are pattern recognition receptors that recognize molecular structures derived from microbes and initiate innate immunity. TLRs have two downstream signaling pathways, the MyD88- and TRIF-dependent pathways. Dysregulated activation of TLRs is closely linked to increased risk of many chronic diseases. Previously, we synthesized fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1- yl)-2-butenoate (IPOP), which contains a fumaric acid isopropyl ester and pyrrolidinone, and demonstrated that it inhibits the activation of nuclear factor kappa B by inhibiting the MyD88-dependent pathway of TLRs. However, the effect of IPOP on the TRIF-dependent pathway remains unknown. Here, we report the effect of IPOP on signal transduction via the TRIF-dependent pathway of TLRs. IPOP inhibited lipopolysaccharide- or polyinosinic-polycytidylic acid-induced interferon regulatory factor 3 activation, as well as interferon- inducible genes such as interferon inducible protein-10. These results suggest that IPOP can modulate the TRIF-dependent signaling pathway of TLRs, leading to decreased inflammatory gene expression.
authors.affiliation: Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan, Korea.
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Shin
authors.forename: In Soon
authors.initials: IS
authors.lastname: Min
authors.forename: Kwang Oh
authors.initials: KO
authors.lastname: Koh
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyung-Sun
authors.initials: HS
authors.lastname: Youn
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D005650:Fumarates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002087:Butyrates; D005650:Fumarates; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011760:Pyrrolidinones; D051193:Toll-Like Receptors; C568139:isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate; D008156:Luciferases; D011070:Poly I-C