Oncostatin M is a potent stimulator of alpha1-antitrypsin secretion in lung epithelial cells: modulation by transforming growth factor-beta and interferon-gamma.
alpha1-Antitrypsin (alpha1-AT) plays a key role in lung homeostasis. Although the hepatocyte is considered as the primary source of alpha1-AT, we have previously demonstrated that rat alveolar epithelial type II cells as well as the human A549 cell line synthesize alpha1-AT, suggesting its local production within the lung. In the present study, we showed that oncostatin M, as opposed to interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or IL-6, is a potent stimulator of alpha1-AT synthesis in the human A549 cell line. The oncostatin M-induced alpha1-AT secretion is modulated by interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) at both the protein and mRNA levels. IFN-gamma decreases oncostatin M-induced alpha1-AT secretion. By contrast, TGF-beta 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.
Boutten
A
A
Services de Biochimie A et de Pneumologie, INSERM U408, Hôpital Bichat, Paris; and U.F.R. Sciences Pharmaceutiques, Chatenay-Malabry, France.
Venembre
P
P
Seta
N
N
Hamelin
J
J
Aubier
M
M
Durand
G
G
Dehoux
M S
MS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology; D008297:Male; D053683:Oncostatin M; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D017077:Culture Media, Conditioned; D016207:Cytokines; C508351:OSM protein, human; D010455:Peptides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D016212:Transforming Growth Factor beta; D000515:alpha 1-Antitrypsin; D053683:Oncostatin M; D003907:Dexamethasone; D007371:Interferon-gamma