Influence of IFN-{gamma} on gene expression in normal human bronchial epithelial cells: modulation of IFN-{gamma} effects by dexamethasone

• Published in: Physiological genomics 2005-09, Vol.23 (1), p.28
• Main Authors: Pawliczak, Rafal, Logun, Carolea, Madara, Patricia, Barb, Jennifer, Suffredini, Anthony F, Munson, Peter J, Danner, Robert L, Shelhamer, James H
• Format: Article
• Language: English
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00011.2005

1 Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland; 2 Department of Allergy and Clinical Immunology, Medical University of Lodz, Lodz, Poland; and 3 Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland Interferon gamma (IFN- ) plays a role in a variety of lung inflammatory responses, and corticosteroids are frequently employed as a treatment in these conditions. Therefore, the effect of IFN- , of the corticosteroid dexamethasone (Dex), or of both on gene expression was studied in normal human bronchial epithelial (NHBE) cells. NHBE cells were exposed to medium alone, IFN- (300 U/ml), Dex (10 –7 M), or both IFN- and Dex for 8 or 24 h. Gene expression was examined using oligonucleotide microarrays. A principal components analysis demonstrated that the IFN- treatment effect was the primary source of differences in the data. With a 5% false discovery rate, of the 66 genes upregulated by IFN- by twofold or greater at 8 h and 287 genes upregulated at 24 h, coincubation with Dex inhibited the expression of 2 genes at 8 h and 45 genes at 24 h. Prominent among these were cytokines and secreted proteins. Dex cotreatment increased expression of 65 of the 376 genes that were inhibited by IFN- by 50% at 24 h. The majority of these genes encode cell cycle or nuclear proteins. Dex alone increased the expression of only 22 genes and inhibited the expression of 7 genes compared with controls at 24 h. The effect of Dex on IFN- -induced changes suggests a specific, targeted effect on IFN- responses that is substantially greater than the effect of Dex alone. Dex had little effect on the immediate early response to IFN- but a significant effect on the late responses. interferon; inflammation, cytokines, lung cells, corticosteroids, transcriptional regulation