title: Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells.
abstract: Heme oxygenase-1 (HO-1) has potent anti-inflammatory activity and recognized vascular protective effects. We have recently described the expression and vascular protective effects of an anti-inflammatory interleukin (IL-19), in vascular smooth muscle cells (VSMC) and injured arteries. The objective of this study was to link the anti-inflammatory effects of IL-19 with HO-1 expression in resident vascular cells. IL-19 induced HO-1 mRNA and protein in cultured human VSMC, as assayed by quantitative RT-PCR, immunoblot, and ELISA. IL-19 does not induce HO-1 mRNA or protein in human endothelial cells. IL-19 activates STAT3 in VSMC, and IL-19-induced HO-1 expression is significantly reduced by transfection of VSMC with STAT3 siRNA or mutation of the consensus STAT binding site in the HO-1 promoter. IL-19 treatment can significantly reduce ROS-induced apoptosis, as assayed by Annexin V flow cytometry. IL-19 significantly reduced ROS concentrations in cultured VSMC. The IL-19-induced reduction in ROS concentration is attenuated when HO-1 is reduced by siRNA, indicating that the IL-19-driven decrease in ROS is mediated by HO-1 expression. IL-19 reduces vascular ROS in vivo in mice treated with TNFα. This points to IL-19 as a potential therapeutic for vascular inflammatory diseases and a link for two previously unassociated protective processes: Th2 cytokine-induced anti-inflammation and ROS reduction.
authors.affiliation: Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Khatuna
authors.initials: K
authors.lastname: Gabunia
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ellison
authors.forename: Harrinder
authors.initials: H
authors.lastname: Singh
authors.forename: Prasun
authors.initials: P
authors.lastname: Datta
authors.forename: Sheri E
authors.initials: SE
authors.lastname: Kelemen
authors.forename: Victor
authors.initials: V
authors.lastname: Rizzo
authors.forename: Michael V
authors.initials: MV
authors.lastname: Autieri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D014657:Vasculitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C421250:IL19 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1