title: Suppression of Toll-Like Receptor 4 Dimerization by 1-[5-Methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine.
abstract: Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and triggers the activation of myeloid differention factor 88 (MyD88) and the Toll/interleukin-1 receptor domain-containing adapter, inducing interferon-β (TRIF)-dependent major downstream signaling pathways. To evaluate the therapeutic potential of 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. Here, we investigated whether MNP modulates the TLR4 signaling pathways and which anti-inflammatory target in TLR4 signaling is regulated by MNP. MNP inhibited the activation of nuclear factor-κB (NF-κB) induced by LPS (TLR4 agonist), and it also inhibited the expression of cyclooxygenase-2 and inducible nitric oxide synthase. MNP inhibited LPS-induced NF-κB activation by targeting TLR4 dimerization in addition to IKKβ. These results suggest that MNP can modulate the TLR4 signaling pathway at the receptor level to decrease inflammatory gene expression.
authors: Department of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Sang-Il
authors: SI
authors: Ahn
authors: Department of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Ji-Soo
authors: JS
authors: Kim
authors: Department of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Gyo-Jeong
authors: GJ
authors: Gu
authors: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Hyeon-Myeong
authors: HM
authors: Shin
authors: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Ah-Yeon
authors: AY
authors: Kim
authors: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea.
authors: Hyun-Jin
authors: HJ
authors: Shim
authors: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
authors: Yeon Joo
authors: YJ
authors: Kim
authors: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
authors: Kwang Oh
authors: KO
authors: Koh
authors: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
authors: Joo Yang
authors: JY
authors: Mang
authors: Department of Chemistry, College of Natural Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
authors: Dae Young
authors: DY
authors: Kim
authors: Department of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea. hyoun@sch.ac.kr.|Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan, Republic of Korea. hyoun@sch.ac.kr.
authors: Hyung-Sun
authors: HS
authors: Youn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009574:Nitro Compounds / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C000615778:1-(5-methoxy-2-(2-nitrovinyl)phenyl)pyrrolidine; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009574:Nitro Compounds; D011759:Pyrrolidines; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase
keywords: 1-[5-Methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine; Inflammation; Lipopolysaccharide; NF-κB; Toll-like receptor