ONCOSTATIN-M IS A POTENT STIMULATOR OF ALPHA(1)-ANTITRYPSIN SECRETIONIN LUNG EPITHELIAL-CELLS - MODULATION BY TRANSFORMING-GROWTH-FACTOR-BETA AND INTERFERON-GAMMA
A. Boutten et al., ONCOSTATIN-M IS A POTENT STIMULATOR OF ALPHA(1)-ANTITRYPSIN SECRETIONIN LUNG EPITHELIAL-CELLS - MODULATION BY TRANSFORMING-GROWTH-FACTOR-BETA AND INTERFERON-GAMMA, American journal of respiratory cell and molecular biology, 18(4), 1998, pp. 511-520
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.