title: Suppressive effects of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine on the Toll-like receptor signaling pathways.
abstract: When various pathogens invade a host, toll-like receptors (TLRs) play a significant role in recognizing the pathogen-associated molecular patterns carried by the pathogens to induce innate immune reaction, followed by acquired immunity reaction. 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. To evaluate the therapeutic potential of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine (FPP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. FPP inhibited the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) induced by TLR agonists, as well as inhibited the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. FPP also inhibited the activation of NF-κB and IRF3 when induced by the overexpression of downstream signaling components of the TLRs. As a result, FPP has potential to become a new therapeutic drug for many inflammatory diseases.
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: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Lim
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: Chae-Yeon
authors.initials: CY
authors.lastname: Hong
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 Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Jeong
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: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000819:agonists; D014753:Vinyl Compounds / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C000601182:1-(4-fluoro-2-(2-nitrovinyl)phenyl)pyrrolidine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054357:Chemokine CXCL10; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; D011759:Pyrrolidines; D051193:Toll-Like Receptors; D014753:Vinyl Compounds; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Cyclooxygenase-2; IRF3; Inducible nitric oxide synthase; NF-κB; Toll-like receptor