Interleukin-19 (IL-19) induces Heme Oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells

Khatuna Gabunia, Stephen P. Ellison, Harrinder Singh, Prasun Datta, Sheri E. Kelemen, Victor Rizzo, Michael Autieri

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish
Pages (from-to)2477-2484
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number4
DOIs
StatePublished - Jan 20 2012

Keywords

  • Animals
  • Apoptosis/drug effects
  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic/drug effects
  • Heme Oxygenase-1/biosynthesis
  • Humans
  • Interleukins/genetics
  • Mice
  • Muscle, Smooth, Vascular/immunology
  • Myocytes, Smooth Muscle/immunology
  • RNA, Messenger/biosynthesis
  • Reactive Oxygen Species/immunology
  • Response Elements/physiology
  • STAT3 Transcription Factor/genetics
  • Th2 Cells/immunology
  • Tumor Necrosis Factor-alpha/immunology
  • Vasculitis/genetics

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