Gamma-glutamyltransferase catabolism of S-nitroso-glutathione modulates IL-8 expression in cystic fibrosis bronchial epithelial cells (Articolo in rivista)

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  • Gamma-glutamyltransferase catabolism of S-nitroso-glutathione modulates IL-8 expression in cystic fibrosis bronchial epithelial cells (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Alternative label
  • A. Corti, G. Bergamini, M. Menegazzi, S. Piaggi, E. Bramanti, I. Scataglini, S. Cianchetti, P. Paggiaro, P. Melotti and P. A. (2013)
    Gamma-glutamyltransferase catabolism of S-nitroso-glutathione modulates IL-8 expression in cystic fibrosis bronchial epithelial cells
    in Free radical biology & medicine; Pergamon Press, Oxford (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • A. Corti, G. Bergamini, M. Menegazzi, S. Piaggi, E. Bramanti, I. Scataglini, S. Cianchetti, P. Paggiaro, P. Melotti and P. A. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • in press (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Patologia Sperimentale, Università di Pisa, Scuola Medica - Pisa; (1) Centro Fibrosi Cistica, Azienda Ospedaliera di Verona, Verona; (2) Dipartimento di Scienze Morfologiche e Biomediche, Università di Verona; (3) National Research Council of Italy, C.N.R., Istituto di Chimica dei Composti Organo Metallici-ICCOM-UOS Pisa; (4) Dipartimento Cardio Toracico e Vascolare, Università di Pisa. (literal)
Titolo
  • Gamma-glutamyltransferase catabolism of S-nitroso-glutathione modulates IL-8 expression in cystic fibrosis bronchial epithelial cells (literal)
Abstract
  • Background: S-Nitrosoglutathione (GSNO) is an endogenous nitrosothiol involved in several pathophysiological processes. A role of GSNO has been envisaged in the expression of inflammatory cytokines such as IL-8, however conflicting results have been reported. Gamma-glutamyltransferase (GGT) enzyme activity can hydrolyze the gamma-glutamyl bond present in GSNO molecule thus greatly accelerating the release of bioactive nitric oxide (NO). Expression of GGT is induced by oxidative stress, and activated neutrophils contribute to GGT in cystic fibrosis (CF) lung exudates by releasing GGT-containing microvescicles. The present study was aimed to evaluate the effect of GSNO catabolism by GGT on production of IL-8 in CFTR-mutated IB3-1 bronchial cells. Principal Findings: The rapid, GGT-catalysed catabolism of GSNO caused a decrease of both basal and LPS-stimulated IL-8 production in IB3-1 cells, by modulating both NF-kB and ERK1/2 pathways, along with a decrease of cell proliferation. On the contrary, slow non-catalysed decomposition of GSNO produced a significant increase of both cell proliferation and expression of IL-8, the latter possibly through p38-mediated stabilization of IL-8 mRNA. Conclusions: Our data suggest that differential GSNO catabolism by GGT enzyme activity can downregulate production of IL-8 in CF cells. Hence, the role of GGT activity and the use of GGT inhibitors should be considered when evaluating GSNO for both in vitro and in vivo studies, the more so in the case of GSNO based therapies. (literal)
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