Interferon-γ inhibits transforming growth factor-β 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, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Because interferon (IFN)-γ may attenuate pulmonary fibrosis, we hypothesized that IFN-γ may regulate transforming growth factor (TCF)-β production by airway epithelial cells. Human bronchial epithelial cells (HBECs) were incubated with IFN-γ ± TGF-β1, -β;3, or interleukin (IL)-1β, platelet-derived growth factor (PDGF), epidermal growth factor, and IL-4. TGF-β2 protein was measured by enzyme-linked immunosorbent assay and mRNA expression for TGF-β2, 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-β1 and 3, IL-1β, PDGF, and IL-4 enhanced TGF-β2 release by HBECs (P < 0.01). IFN-γ reduced basal and TGF-β or IL-4-augmented TGF-β2 release, but had little effect on IL-1β- or PDGF-augmented TGF-β2 release. IFN-γ stimulated Smad 7 protein and mRNA expression. Smad 7-specific siRNA decreased Smad 7 protein expression both in control and IFN-γ-treated cells. The inhibitory effect of IFN-γ on TGF-β2 production was abrogated when the HBECs were treated with Smad 7 siRNA. These results suggest that IFN-γ downregulates TGF-β2 production by HBECs by regulating Smad 7. Through this mechanism, IFN-γ may play an important role in tissue remodeling.

Original languageEnglish (US)
Pages (from-to)816-822
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume30
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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