title: Apocynin Suppresses Lipopolysaccharide-Induced Inflammatory Responses Through the Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells.
abstract: Apocynin, an inhibitor of NADPH oxidase, exhibits anti-inflammatory properties in ulcerative colitis. However, the underlying mechanism by which apocynin exerts this effect has not been clearly demonstrated. The objective of this study was to elucidate the anti-inflammatory mechanism of apocynin in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. Apocynin inhibited LPS-induced extracellular secretion of the pro-inflammatory mediators, nitric oxide (NO) and PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2. Apocynin also suppressed LPS-induced secretion of the pro-inflammatory cytokine, tumor necrosis factor-α and LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. To elucidate the underlying anti-inflammatory mechanism of apocynin, the involvement of the mitogen-activated protein (MAP) kinases, c-jun N-terminal kinase, extracellular signal-regulated kinases, and p38 was examined. Apocynin attenuated LPS-induced activation of all three MAP kinases in a concentration-dependent manner. The present study demonstrates apocynin exerts anti-inflammatory activity via the suppression of MAP kinase signaling pathways in LPS-challenged RAW264.7 macrophage cells. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Chang Don
authors.initials: CD
authors.lastname: Kang
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C056165:acetovanillone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: COX-2; MAP kinases; RAW264.7 cells; apocynin; lipopolysaccharide