Interleukin-4- and interleukin-13-enhanced transforming growth factor-β2 production in cultured human bronchial epithelial cells is attenuated by interferon-γ

Cytokines derived from lymphocytes are believed to play key roles in a variety of diseases, including airway diseases such as asthma. The current study was designed to evaluate the hypothesis that cytokines derived from Th2 cells, interleukin (IL)-4 and IL-13, might contribute to tissue remodeling by modulating the production of transforming growth factor (TGF)-β. In addition, the ability of interferon (IFN)-γ, a cytokine derived from Th1 cells that can antagonize many effects of IL-4 and IL-13, was also assessed for its effects on TGF-β production. IL-4 and IL-13 both stimulated production of TGF-β2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-β2 were detected. Neither TGF-β1 nor TGF-β3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF-β isoform from human lung fibroblasts. IFN-γ reduced both basal, IL-4-, and IL-13-stimulated release of TGF-β2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN-γ on TGF-β2 release were paralleled by mRNA levels, as assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In summary, the Th2-derived cytokines, IL-4 and IL-13, can stimulate production of TGF-β from airway epithelial cells but not from lung fibroblasts. IFN-γ, in contrast, can inhibit TGF-β2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF-β release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.