Interferon- Inhibits Transforming Growth Factor- Production in Human Airway Epithelial Cells by Targeting Smads

Because interferon (IFN)may attenuate pulmonary fibrosis, we hypothesized that IFNmay regulate transforming growth factor (TGF)production by airway epithelial cells. Human bronchial epithelial cells (HBECs) were incubated with IFNTGF1, 3, or interleukin (IL)-1 , platelet-derived growth factor (PDGF), epidermal growth factor, and IL-4. TGF2 protein was measured by enzyme-linked immunosorbent assay and mRNA expression for TGF2, 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 TGF1 and 3, IL-1 , PDGF, and IL-4 enhanced TGF2 release by HBECs (P 0.01). IFNreduced basal and TGFor IL-4–augmented TGF2 release, but had little effect on IL-1 – or PDGF-augmented TGF2 release. IFNstimulated Smad 7 protein and mRNA expression. Smad 7–specific siRNA decreased Smad 7 protein expression both in control and IFN–treated cells. The inhibitory effect of IFNon TGF2 production was abrogated when the HBECs were treated with Smad 7 siRNA. These results suggest that IFNdownregulates TGF2 production by HBECs by regulating Smad 7. Through this mechanism, IFNmay play an important role in tissue remodeling.