title: Dual specificity phosphatase 1 regulates human inducible nitric oxide synthase expression by p38 MAP kinase.
abstract: The role of dual specificity phosphatase 1 (DUSP1) in inducible nitric oxide synthase (iNOS) expression in A549 human pulmonary epithelial cells, J774 mouse macrophages and primary mouse bone marrow-derived macrophages (BMMs) was investigated. iNOS expression was induced by a cytokine mixture (TNF, IFNγ and IL-1β) in A549 cells and by LPS in J774 cells, and it was inhibited by p38 MAPK inhibitors SB202190 and BIRB 796. Stimulation with cytokine mixture or LPS enhanced also DUSP1 expression. Down-regulation of DUSP1 by siRNA increased p38 MAPK phosphorylation and iNOS expression in A549 and J774 cells. In addition, LPS-induced iNOS expression was enhanced in BMMs from DUSP1((-/-)) mice as compared to that in BMMs from wild-type mice. The results indicate that DUSP1 suppresses iNOS expression by limiting p38 MAPK activity in human and mouse cells. Compounds that enhance DUSP1 expression or modulate its function may be beneficial in diseases complicated with increased iNOS-mediated NO production.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Turpeinen
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Ville
authors.initials: V
authors.lastname: Taimi
authors.forename: Taina
authors.initials: T
authors.lastname: Heittola
authors.forename: Outi
authors.initials: O
authors.lastname: Sareila
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Clark
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Riku
authors.initials: R
authors.lastname: Korhonen
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1