Am. J. Respir. Cell Mol. Biol., Volume 18, Number 4, April, 1998 511-520

Oncostatin M Is a Potent Stimulator of ₁-Antitrypsin Secretion in Lung Epithelial Cells: Modulation by Transforming Growth Factor- and Interferon-

Anne Boutten, Philippe Venembre, Nathalie Seta, Jocelyne Hamelin, Michel Aubier, Geneviève Durand, and Monique S. Dehoux

Services de Biochimie A et de Pneumologie, INSERM U408, Hôpital Bichat, Paris; and U.F.R. Sciences Pharmaceutiques, Chatenay-Malabry, France

₁-Antitrypsin (₁-AT) plays a key role in lung homeostasis. Although the hepatocyte is considered as the primary source of ₁-AT, we have previously demonstrated that rat alveolar epithelial type II cells as well as the human A549 cell line synthesize ₁-AT, suggesting its local production within the lung. In the present study, we showed that oncostatin M, as opposed to interleukin-1 (IL-1), tumor necrosis factor- (TNF-), or IL-6, is a potent stimulator of ₁-AT synthesis in the human A549 cell line. The oncostatin M-induced ₁-AT secretion is modulated by interferon- (IFN-) and transforming growth factor- (TGF-) at both the protein and mRNA levels. IFN- decreases oncostatin M-induced ₁-AT secretion. By contrast, TGF- in combination with oncostatin M induces a dramatic and synergistic upregulation that is not observed in the HepG2 hepatocyte cell line. Our results suggest that during an inflammatory process, alveolar epithelial cells may contribute to the antiprotease defense within the lung.

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