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Down modulation of IFN-gamma signaling in alveolar macrophages isolated from smokers.

Dhillon NK, Murphy WJ, Filla MB, Crespo AJ, Latham HA, O'Brien-Ladner A

Division of Pulmonary and Critical Care Medicine, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.

The master cytokine, IFN-gamma possesses a wide spectrum of biological effects and is crucial for development of the highly activated macrophage phenotype characteristically found during inflammation. However, no data exists regarding the potential influence of cigarette smoke on the status of the expression of the cell surface receptor for IFN-gamma (IFN-gammaR) on alveolar macrophages (AM) of smokers. Here in, we report reduction in the expression of the IFN-gammaR alpha-chain on AM of cigarette smokers, when compared with non-smokers. Ensuing from the loss of receptor expression on the AM of smokers there was a decrease in IFN-gamma-mediated cell signaling. This included a decrease in the phosphorylation of signal transducer and activator of transcription (STAT)-1 and induction of interferon regulatory factor (IRF)-1. Further, diminished activation/induction of transcription factors did not appear to result from induction of known members of the 'suppressors of cytokine signaling (SOCS)' family. Decreased IFN-gamma signal transduction in AM from smokers may have an important implication regarding the use of therapeutic IFN-gamma in the lungs of patients that develop respiratory disorders as a result of tobacco use.

Published 12 May 2009 in Toxicol Appl Pharmacol, 237(1): 22-8.
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