title: Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NFκB and MAPK pathways in RAW264.7 cells.
abstract: In the present study, we confirmed the ability of M. hyopneumoniae to induce the secretion of large amount of proinflammatory cytokine and nitric oxide (NO) in murine macrophage RAW 264.7 cells. Moreover, M. hyopneumoniae-induced activation of the MAPK and NF-кB pathways by phosphorylation of ERK1/2, p38 and JNK/SAPK and by dissociation of IκB from NF-κB. Translocation of transcription factor NF-κB and its binding was confirmed through western blot and electromobility shift assay. From these results, we further hypothesized that these signal proteins were involved in M. hyopneumoniae-induced proinflammatory cytokines and NO productions in macrophages. Hence, we utilized specific blockers of MAPK and NF-κB to investigate the signaling pathway involvement in cytokine and NO production through pharmacological approaches. The results demonstrated significant inhibition of TNF-α, IL-1β, IL-6 and NO by MAPK inhibitors. NF-κB inhibitor PDTC significantly inhibited IL-1β and NO production. These findings contribute to the understanding of the mechanisms of immune reactivity and may ultimately prove useful in the development of new therapeutic strategies. In summary, we found critical evidence for the involvement of NF-κB and MAPK signaling pathways in the upregulation of proinflammatory cytokine and NO induced by M. hyopneumoniae.
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, South Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Hwang
authors.forename: Dereje
authors.initials: D
authors.lastname: Damte
authors.forename: Joong-Su
authors.initials: JS
authors.lastname: Lee
authors.forename: Elias
authors.initials: E
authors.lastname: Gebru
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chang
authors.forename: Henrique
authors.initials: H
authors.lastname: Cheng
authors.forename: Byeong-Yeal
authors.initials: BY
authors.lastname: Jung
authors.forename: Man-Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D045705:Mycoplasma hyopneumoniae / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D045729:Pneumonia of Swine, Mycoplasmal / Q000276:immunology* / Q000382:microbiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013552:Swine; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D002070:Butadienes; D016207:Cytokines; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011759:Pyrrolidines; D013859:Thiocarbamates; C113580:U 0126; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580