Protective role of retinoic acid from antiproliferative action of TNF-alpha on lung epithelial cells.
Tumor necrosis factor (TNF)-alpha is a key molecule in lung inflammation. We have established the insulin-like growth factor binding protein 2 (IGFBP-2) as a marker associated with the growth arrest of lung alveolar epithelial cells (AEC). Here, we studied the effects of TNF-alpha on AEC proliferation and the putative protective role of retinoic acid (RA). We documented an antiproliferative action of TNF-alpha that was reversible only at 24 h and then became irreversible with induction of apoptosis. TNF-alpha treatment was associated with a dramatic induction of IGFBP-2. To discover the mechanism of action of IGFBP-2, we further tested the mitogenic potential of IGF-I to counteract TNF-alpha inhibition. Addition of IGF-I to the TNF-alpha containing medium did not stimulate proliferation, whereas des(1-3)IGF-I, an analog of IGF-I that bears low affinity for IGFBPs, was able to restore cell growth. Interestingly, we observed that RA abrogated TNF-alpha-induced growth arrest and that this effect was associated with a dramatic decrease in IGFBP-2 expression. These results suggest a protective role of RA from TNF-alpha antiproliferative action, through mechanisms involving modulation of IGFBP-2 production.
Besnard
Valérie
V
Département de Pneumologie Pédiatrique, Institut National de la Santé et de la Recherche Médicale U515, Hôpital Trousseau Assistance Publique-Hôpitaux de Paris, Université Paris VI, 26 Ave Dr. Netter, 75012 Paris, France.
Nabeyrat
Elodie
E
Henrion-Caude
Alexandra
A
Chadelat
Katarina
K
Perin
Laurence
L
Le Bouc
Yves
Y
Clement
Annick
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004347:Drug Interactions; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011014:Pneumonia / Q000188:drug therapy; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018971:Insulin-Like Growth Factor Binding Protein 2; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C058957:insulin-like growth factor 1, des-(1-3)-; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I