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Azithromycin decreases Glutathione-S-Transferase T1 (GSTT1) and M1 (GSTM1) expression and activity in cystic fibrosis airway epithelial cells  (2009)

Authors:
Bergamini G. , Cigana C., Sorio C., Della Peruta M., Assael B.M., Melotti P.
Title:
Azithromycin decreases Glutathione-S-Transferase T1 (GSTT1) and M1 (GSTM1) expression and activity in cystic fibrosis airway epithelial cells
Year:
2009
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Nations of authors:
ITALIA
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
American Journal of Respiratory Cell & Molecular Biology
ISSN of journal:
1044-1549
N° Volume:
41
Number or Folder:
2
Page numbers:
199-206
Code PMID:
19097986
Keyword:
azithromycin, glutathione S-transferases, cystic fibrosis, airway cells
Short description of contents:
Abstract Anti-inflammatory properties of azithromycin (AZM) have been proposed as possible mechanism of clinical beneficial effects in cystic fibrosis (CF) patients. Altered glutathione (GSH) transport in cystic fibrosis transmembrane regulator protein (CFTR)-deficient cells leads to the occurrence of oxidative stress that finally induces glutathione S-transferase (GST) activity. The present investigation was aimed to verify the effects of AZM on GST activity and expression in CF airway cells in vitro and in vivo. AZM exposure significantly decreased GSTT1 and GSTM1 mRNA and protein expression in IB3-1, restoring the levels to those observed in non-CF C38 cells, that also express lower levels of γ-glutamyltransferase (GGT) activity than IB3-1. In another CF cell line, 2CFSMEo-, AZM produced 45% reduction in GSTT1 and GSTM1 mRNA levels. AZM reduced GST activity of about 25% and 40% in IB3-1 and 2CFSMEo- cells, respectively. GSTP1 was similarly expressed in all CF and non-CF cells and was unaffected by AZM. The anti-inflammatory cytokine interleukin (IL)-10 down-modulated GST activity at similar levels, supporting a link between GST inhibition and anti-inflammatory properties of AZM. In bronchoalveolar lavage fluid of CF mice homozygous for the F508del mutation, GSTM1 protein levels were undetectable following AZM treatment. The association between increased GST expression and activity together with its reversal by AZM treatment in vitro and in vivo suggest novel anti-oxidant properties for this drug. The issue whether decreased GST activity may directly concur to anti-inflammatory properties of AZM or is rather a marker of the oxidative status of CF cells will require additional studies.
Web page:
http://ajrcmb.atsjournals.org/cgi/reprint/2008-0013OCv1
Product ID:
55287
Handle IRIS:
11562/-327809
Deposited On:
September 9, 2009
Last Modified:
September 9, 2009
Bibliographic citation:
Bergamini G. , Cigana C., Sorio C., Della Peruta M., Assael B.M., Melotti P., Azithromycin decreases Glutathione-S-Transferase T1 (GSTT1) and M1 (GSTM1) expression and activity in cystic fibrosis airway epithelial cells «American Journal of Respiratory Cell & Molecular Biology» , vol. 41 , n. 22009pp. 199-206

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