help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 12, 2004, doi:10.1165/rcmb.2002-0249OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0249OCv1
30/6/816    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wen, F.-Q.
Right arrow Articles by Rennard, S. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wen, F.-Q.
Right arrow Articles by Rennard, S. I.
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




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Q. Wu, R. J. Martin, J. G. Rino, S. Jeyaseelan, R. Breed, and H. W. Chu
A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice
Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1064 - L1072.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
F Rieder, J Brenmoehl, S Leeb, J Scholmerich, and G Rogler
Wound healing and fibrosis in intestinal disease
Gut, January 1, 2007; 56(1): 130 - 139.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. G. R. Thompson, J. D. Mih, T. B. Krasieva, B. J. Tromberg, and S. C. George
Epithelial-derived TGF-beta2 modulates basal and wound-healing subepithelial matrix homeostasis
Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1277 - L1285.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. H. Kim, H. Y. Kim, S. Kim, J.-H. Chung, W. S. Park, and D. H. Chung
Natural Killer T (NKT) Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis by Producing Interferon-{gamma}
Am. J. Pathol., November 1, 2005; 167(5): 1231 - 1241.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
M. A Pacanowski and G. W Amsden
Interferon Gamma-1b in the Treatment of Idiopathic Pulmonary Fibrosis
Ann. Pharmacother., October 1, 2005; 39(10): 1678 - 1686.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. E. Dierksheide, R. A. Baiocchi, A. K. Ferketich, S. Roychowdhury, R. P. Pelletier, C. F. Eisenbeis, M. A. Caligiuri, and A. M. VanBuskirk
IFN-{gamma} gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice
Blood, February 15, 2005; 105(4): 1558 - 1565.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society. 		  CCM abstracts