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Involvement of Syk kinase in TNF-induced nitric oxide production by airway epithelial cells

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [1];  [1];  [1];  [2];  [2];  [1]
  1. Department of Medicine, University of Alberta, Edmonton, Alta. (Canada)
  2. University of Pennsylvania School of Medicine, Philadelphia, PA (United States)
We have recently found that Syk is widely expressed in lung epithelial cells (EC) and participates in {beta}1 integrin signaling. In this study, we assessed the role of Syk in regulation of NO production. Stimulation of human bronchial EC line HS-24 by TNF caused an increased expression of inducible nitric oxide synthase (iNOS). Inhibition of Syk using siRNA or piceatannol down-regulated the iNOS expression and reduced NO production. This effect occurred in EC simultaneously stimulated via {beta}1 integrins, suggesting that TNF and {beta}1 integrins provide co-stimulatory signals. Inhibition of Syk down-regulated TNF-induced p38 and p44/42 MAPK phosphorylation and nuclear translocation of p65 NF-{kappa}B. Thus, TNF-induced activation of pro-inflammatory signaling in EC leading to enhanced expression of iNOS and NO production was dependent on Syk. Syk-mediated signaling regulates NO production at least partly via activating the MAPK cascade. Understanding the role of Syk in airway EC may help in developing new therapeutic tools for inflammatory lung disorders.
OSTI ID:
20857918
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 351; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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