Cytokines, growth factors, and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde, and LPS

Inflammatory mediators, including cytokines, growth factors, and reactive o xygen species, are associated with the pathology of chronic liver disease. In the liver, cytokine and growth factor secretion are usually associated w ith nonparenchymal cells. particularly Kupffer cells. In the present studie s, the effect of 24 and 72 h administration of ethanol (50 mM), acetaldehyd e (175 mu M). and LPS (1 mu g/ml) were studied on the expression and secret ion of TNF-alpha, IL-1 beta, IL-6, and TGF-beta(1), lipid peroxidation dama ge and glutathion content in HepG2 cell cultures. A 24 h exposure to ethano l induced the expression of TNF-alpha and TGF-beta(1), and the secretion of IL-1 beta and TGF-beta(1). With the same period of treatment, acetaldehyde markedly increased TNF-alpha expression, and stimulated IL-1 beta secretio n, while LPS exposure induced the expression of TNF-alpha, IL-6, and TGF-be ta(1), and the secretion of IL-1 beta, IL-6, and TGF-beta(1). A reduced in TNF-alpha response and TGF-beta(1) expression were observed after 72 h expo sure to ethanol. A 72 h acetaldehyde exposure decreased markedly TNF-alpha expression and stimulated a previously absent TGF-beta(1) response. With th e same time of exposure, LPS reduced slightly TGF-beta(1) expression, and d ecreased its secretion. IL-1 beta and IL-6 were not detected under 72 h exp osure conditions. Lipid peroxidation damage was increased in all treatments , but higher values were found in 72 h treatments. Glutathion content dimin ished in all treatments. These findings suggest that HepG2 cells. independe nt of other cells such as Kupffer or macrophages, participate in a differen tial cytokine, growth factor and oxidative stress response. which differs a ccording to the toxic agent and the time of exposure. (C) 1999 Elsevier Sci ence Ireland Ltd. All rights reserved.