title: Suppression of TLRs signaling pathways by 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine.
abstract: Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-κB and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the MyD88- or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Ahn
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Ji-Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Hyeon-Myeong
authors.initials: HM
authors.lastname: Shin
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Ah-Yeon
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Gyo-Jeong
authors.initials: GJ
authors.lastname: Gu
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Shim
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Kwang Oh
authors.initials: KO
authors.lastname: Koh
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Joo Yang
authors.initials: JY
authors.lastname: Mang
authors.affiliation: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea; Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea. Electronic address: hyoun@sch.ac.kr.
authors.forename: Hyung-Sun
authors.initials: HS
authors.lastname: Youn
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D054357:Chemokine CXCL10; D051546:Cyclooxygenase 2; D050838:Interferon Regulatory Factor-3; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D009574:Nitro Compounds; D011759:Pyrrolidines; D051193:Toll-Like Receptors; C000615778:1-(5-methoxy-2-(2-nitrovinyl)phenyl)pyrrolidine; C494233:Irf3 protein, mouse; C476286:Ticam1 protein, mouse; C077623:Ptgs2 protein, mouse
keywords: 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine; MyD88; Nuclear factor-κB; TRIF; Toll-like receptor