Interferon-gamma inhibits transforming growth factor-beta production in human airway epithelial cells by targeting Smads
| Autor: | Stephen I. Rennard, Qiuhong Fang, Xiangde Liu, Shinji Abe, Lidia S. Manouilova, Tetsu Kobayashi, Fu Qiang Wen, Ronald F. Ertl, Tadashi Kohyama, Yusuke Terasaki |
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| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
TGF alpha medicine.medical_treatment Clinical Biochemistry SMAD Respiratory Mucosa Smad7 Protein Interferon-gamma Epidermal growth factor Transforming Growth Factor beta medicine Humans Smad3 Protein RNA Small Interfering Molecular Biology Cells Cultured Platelet-Derived Growth Factor biology Epidermal Growth Factor Growth factor Epithelial Cells Cell Biology Transforming growth factor beta Molecular biology DNA-Binding Proteins Transforming growth factor beta 3 biology.protein Trans-Activators Interleukin-4 Platelet-derived growth factor receptor Transforming growth factor Interleukin-1 |
| Zdroj: | American journal of respiratory cell and molecular biology. 30(6) |
| ISSN: | 1044-1549 |
| Popis: | Because interferon (IFN)-gamma may attenuate pulmonary fibrosis, we hypothesized that IFN-gamma may regulate transforming growth factor (TGF)-beta production by airway epithelial cells. Human bronchial epithelial cells (HBECs) were incubated with IFN-gamma +/- TGF-beta1, -beta3, or interleukin (IL)-1beta, platelet-derived growth factor (PDGF), epidermal growth factor, and IL-4. TGF-beta2 protein was measured by enzyme-linked immunosorbent assay and mRNA expression for TGF-beta2, 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-beta1 and 3, IL-1beta, PDGF, and IL-4 enhanced TGF-beta2 release by HBECs (P < 0.01). IFN-gamma reduced basal and TGF-beta or IL-4-augmented TGF-beta2 release, but had little effect on IL-1beta- or PDGF-augmented TGF-beta2 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-beta2 production was abrogated when the HBECs were treated with Smad 7 siRNA. These results suggest that IFN-gamma down regulates TGF-beta2 production by HBECs by regulating Smad 7. Through this mechanism, IFN-gamma may play an important role in tissue remodeling. |
| Databáze: | OpenAIRE |
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