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 language | English |
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Pages (from-to) | 2477-2484 |
Number of pages | 8 |
Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 4 |
DOIs | |
State | Published - 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