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 journalArticle

11 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

Fingerprint

Vascular Smooth Muscle
Oxidants
Smooth Muscle Myocytes
Lung
NADPH Oxidase
Thioredoxins
Small Interfering RNA
Reactive Oxygen Species
Proteins
Phosphorylation
Protein Carbonylation
Glutaredoxins
interleukin-22
STAT3 Transcription Factor
Phosphopyruvate Hydratase
Mitochondrial Proteins
Tubulin
Growth
Heat-Shock Proteins
Pulmonary Hypertension

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bansal, G., Das, D., Hsieh, C. Y., Wang, Y. H., Gilmore, B. A., Wong, C. M., & Suzuki, Y. J. (2013). IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells. Cellular Signalling, 25(12), 2727-2733. https://doi.org/10.1016/j.cellsig.2013.09.001

IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells. / Bansal, Geetanjali; Das, Dividutta; Hsieh, Cheng Ying; Wang, Yi Hsuan; Gilmore, Brent A.; Wong, Chi Ming; Suzuki, Yuichiro J.

In: Cellular Signalling, Vol. 25, No. 12, 12.2013, p. 2727-2733.

Research output: Contribution to journalArticle

Bansal, G, Das, D, Hsieh, CY, Wang, YH, Gilmore, BA, Wong, CM & Suzuki, YJ 2013, 'IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells', Cellular Signalling, vol. 25, no. 12, pp. 2727-2733. https://doi.org/10.1016/j.cellsig.2013.09.001
Bansal, Geetanjali ; Das, Dividutta ; Hsieh, Cheng Ying ; Wang, Yi Hsuan ; Gilmore, Brent A. ; Wong, Chi Ming ; Suzuki, Yuichiro J. / IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells. In: Cellular Signalling. 2013 ; Vol. 25, No. 12. pp. 2727-2733.
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