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Published ahead of print on January 12, 2004, doi:10.1165/rcmb.2002-0249OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 816-822, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2002-0249OC

Interferon-{gamma} Inhibits Transforming Growth Factor-ß Production in Human Airway Epithelial Cells by Targeting Smads

Fu-Qiang Wen, Xiangde Liu, Tetsu Kobayashi, Shinji Abe, Qiuhong Fang, Tadashi Kohyama, Ronald Ertl, Yusuke Terasaki, Lidia Manouilova and Stephen I. Rennard

Department of Respiratory Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China; Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; and Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan

Address correspondence to: Stephen I. Rennard, M.D., University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198–5885. E-mail:srennard{at}unmc.edu

Because interferon (IFN)-{gamma} may attenuate pulmonary fibrosis, we hypothesized that IFN-{gamma} may regulate transforming growth factor (TGF)-ß production by airway epithelial cells. Human bronchial epithelial cells (HBECs) were incubated with IFN-{gamma} ± TGF-ß1, -ß3, or interleukin (IL)-1ß, platelet-derived growth factor (PDGF), epidermal growth factor, and IL-4. TGF-ß2 protein was measured by enzyme-linked immunosorbent assay and mRNA expression for TGF-ß2, Smad 2, 3, 4, and 7 was evaluated by real-time reverse transcriptase–polymerase chain reaction. Localization of Smads 2, 3, 4, and 7 was evaluated by immunostaining. Exogenous TGF-ß1 and 3, IL-1ß, PDGF, and IL-4 enhanced TGF-ß2 release by HBECs (P < 0.01). IFN-{gamma} reduced basal and TGF-ß or IL-4–augmented TGF-ß2 release, but had little effect on IL-1ß– or PDGF-augmented TGF-ß2 release. IFN-{gamma} stimulated Smad 7 protein and mRNA expression. Smad 7–specific siRNA decreased Smad 7 protein expression both in control and IFN-{gamma}–treated cells. The inhibitory effect of IFN-{gamma} on TGF-ß2 production was abrogated when the HBECs were treated with Smad 7 siRNA. These results suggest that IFN-{gamma} downregulates TGF-ß2 production by HBECs by regulating Smad 7. Through this mechanism, IFN-{gamma} may play an important role in tissue remodeling.

Abbreviations: chronic obstructive pulmonary disease, COPD • epidermal growth factor, EGF • enzyme-linked immunosorbent assay, ELISA • human bronchial epithelial cells, HBEC • interferon-{gamma}, IFN-{gamma} • interleukin, IL • lactate dehydrogenase, LDH • polymerase chain reaction, PCR • platelet-derived growth factor, PDGF • reverse transcriptase, RT • transforming growth factor-ß, TGF-ß




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Copyright © 2004 American Thoracic Society. 		  2009/2010 ATS Fellows Career Development Awards