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

Inflammatory mediators, including cytokines, growth factors, and reactive oxygen species, are associated with the pathology of chronic liver disease. In the liver, cytokine and growth factor secretion are usually associated with nonparenchymal cells, particularly Kupffer cells. In the present studies, the effect of 24 and 72 h administration of ethanol (50 mM), acetaldehyde (175 μM), and LPS (1 μg/ml) were studied on the expression and secretion of TNF-α, IL-1β, IL-6, and TGF-β 1, lipid peroxidation damage and glutathion content in HepG2 cell cultures. A 24 h exposure to ethanol induced the expression of TNF-α and TGF-β 1, and the secretion of IL-1β and TGF-β 1. With the same period of treatment, acetaldehyde markedly increased TNF-α expression, and stimulated IL-1β secretion, while LPS exposure induced the expression of TNF-α, IL-6, and TGF-β 1, and the secretion of IL-1β, IL-6, and TGF-β 1. A reduced in TNF-α response and TGF-β 1 expression were observed after 72 h exposure to ethanol. A 72 h acetaldehyde exposure decreased markedly TNF-α expression and stimulated a previously absent TGF-β 1 response. With the same time of exposure, LPS reduced slightly TGF-β 1 expression, and decreased its secretion. IL-1β and IL-6 were not detected under 72 h exposure conditions. Lipid peroxidation damage was increased in all treatments, but higher values were found in 72 h treatments. Glutathion content diminished in all treatments. These findings suggest that HepG2 cells, independent of other cells such as Kupffer or macrophages, participate in a differential cytokine, growth factor and oxidative stress response, which differs according to the toxic agent and the time of exposure.