Am. J. Respir. Cell Mol. Biol., Volume 26, Number 4, April, 2002 484-490

Interleukin-4- and Interleukin-13-Enhanced Transforming Growth Factor-2 Production in Cultured Human Bronchial Epithelial Cells Is Attenuated by Interferon-

Fu-Qiang Wen, Tadashi Kohyama, Xiangde Liu, Yun Kui Zhu, Hangjun Wang, Hui Jun Kim, Tetsu Kobayashi, Shinji Abe, John R. Spurzem, and Stephen I. Rennard

Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Respiratory Diseases, Jincheng Hospital, Lanzhou, China; Mount Sinai Hospital, Toronto, Ontario, Canada; and Pulmonary Division, Department of Internal Medicine, Seoul Adventist Hospital, Seoul, Korea

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)-. In addition, the ability of interferon (IFN)-, 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- production. IL-4 and IL-13 both stimulated production of TGF-2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-2 were detected. Neither TGF-1 nor TGF-3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF- isoform from human lung fibroblasts. IFN- reduced both basal, IL-4-, and IL-13-stimulated release of TGF-2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN- on TGF-2 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- from airway epithelial cells but not from lung fibroblasts. IFN-, in contrast, can inhibit TGF-2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF- release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.

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