Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1.

ABSTRACT: We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-alpha and IFN-gamma impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRbeta) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-alpha and IFN-gamma (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRalpha nuclear translocation nor GRbeta expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-alpha and IFN-gamma combination but not with cytokine alone, was also completely insensitive to ster

SUBMITTER: Tliba O 

PROVIDER: S-EPMC2274949 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature