alpha(1)-antitrypsin can increase insulin-induced mitogenesis in various fibroblast and epithelial cell lines

alpha(1)-Antitrypsin (AT), the archetypal member of the superfamily of seri ne proteinase inhibitors, inhibits leukocyte elastase activity and thereby can prevent lung damage, Here we show that in fibroblasts from human fetal lung and mouse embryo as well as in certain epithelial cells AT can also en hance the stimulatory effects of insulin on DNA synthesis and cell prolifer ation. Warming of AT at a moderate (41 degrees C) temperature for a longer time (21 h) or at a higher (65 degrees C) temperature for 30 min before tre atment increased its stimulatory effects on both DNA synthesis and activati ng phosphorylation of p42/p44 mitogen-activated protein kinases, The result s suggest that AT may promote regeneration of damaged tissues under pathoph ysiological conditions which are associated with fever. (C) 2000 Federation of European Biochemical Societies.