IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells

Geetanjali Bansal, Dividutta Das, Cheng Ying Hsieh, Yi Hsuan Wang, Brent A. Gilmore, Chi Ming Wong, Yuichiro J. Suzuki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) mediate cell-signaling processes in response to various ligands and play important roles in the pathogenesis of cardiovascular diseases. The present study reports that interleukin-22 (IL-22) elicits signal transduction in vascular smooth muscle cells (SMCs) through a ROS-dependent mechanism. We find that pulmonary artery SMCs express IL-22 receptor alpha 1 and that IL-22 activates STAT3 through this receptor. IL-22-induced signaling is found to be mediated by NADPH oxidase, as indicated by the observations that the inhibition and siRNA knock-down of this enzyme inhibit IL-22 signaling. IL-22 triggers the oxidative modifications of proteins through protein carbonylation and protein glutathionylation. Mass spectrometry identified some proteins that are carbonylated in response to IL-22 stimulation, including α-enolase, heat shock cognate 71. kDa protein, mitochondrial 60. kDa heat shock protein, and cytoplasmic 2 actin and determined that α-tubulin is glutathionylated. Protein glutathionylation and STAT3 phosphorylation are enhanced by the siRNA knock-down of glutaredoxin, while IL-22-mediated STAT3 phosphorylation is suppressed by knocking down thioredoxin interacting protein, an inhibitor of thioredoxin. IL-22 is also found to promote the growth of SMCs via NADPH oxidase. In rats, pulmonary hypertension is found to be associated with increased smooth muscle IL-22 expression. These results show that IL-22 promotes the growth of pulmonary vascular SMCs via a signaling mechanism that involves NADPH oxidase-dependent oxidation.

Original languageEnglish
Pages (from-to)2727-2733
Number of pages7
JournalCellular Signalling
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 2013
Externally publishedYes

Keywords

  • Interleukin-22
  • Reactive oxygen species
  • Redox signaling
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Cell Biology

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