ONCOSTATIN-M IS A POTENT STIMULATOR OF ALPHA(1)-ANTITRYPSIN SECRETIONIN LUNG EPITHELIAL-CELLS - MODULATION BY TRANSFORMING-GROWTH-FACTOR-BETA AND INTERFERON-GAMMA

alpha(1)-Antitrypsin (alpha(1)-AT) plays a key role in lung homeostasi s. Although the hepatocyte is considered as the primary source of alph a(1)-AT, we have previously demonstrated that rat alveolar epithelial type II cells as well as the human A549 cell line synthesize alpha(1)- AT, suggesting its local production within the lung. In the present st udy, we showed that oncostatin M, as opposed to interleukin-1 beta (IL -1 beta), tumor necrosis factor-alpha (TNF-alpha), or IL-6, is a poten t stimulator of alpha(1)-AT synthesis in the human A549 cell line. The oncostatin M-induced alpha(1)-AT secretion is modulated by interferon -gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) at b oth the protein and mRNA levels. IFN-gamma decreases oncostatin M-indu ced alpha(1)-AT secretion. By contrast, TGF-beta in combination with o ncostatin M induces a dramatic and synergistic upregulation that is no t observed in the HepG2 hepatocyte cell line. Our results suggest that during an inflammatory process, alveolar epithelial cells may contrib ute to the antiprotease defense within the lung.