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 microM), and LPS (1 microg/ml) were studied on the expression and secretion of TNF-alpha, IL-1beta, IL-6, and TGF-beta3, lipid peroxidation damage and glutathion content in HepG2 cell cultures. A 24 h exposure to ethanol induced the expression of TNF-alpha and TGF-beta1, and the secretion of IL-1beta and TGF-beta1. With the same period of treatment, acetaldehyde markedly increased TNF-alpha expression, and stimulated IL-1beta secretion, while LPS exposure induced the expression of TNF-alpha, IL-6, and TGF-beta1, and the secretion of IL-1beta, IL-6, and TGF-beta1. A reduced in TNF-alpha response and TGF-beta1 expression were observed after 72 h exposure to ethanol. A 72 h acetaldehyde exposure decreased markedly TNF-alpha expression and stimulated a previously absent TGF-beta1 response. With the same time of exposure, LPS reduced slightly TGF-beta1 expression, and decreased its secretion. IL-1beta 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.
Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, México D.F., Mexico. mcgr@xanum.uam.mx
M C
MC
Gutiérrez-Ruiz
S C
SC
Quiroz
V
V
Souza
L
L
Bucio
E
E
Hernández
I P
IP
Olivares
L
L
Llorente
F
F
Vargas-Vorácková
D
D
Kershenobich
D000079:Acetaldehyde / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis*; D000431:Ethanol / Q000633:toxicity*; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D008070:Lipopolysaccharides; D000431:Ethanol; D000079:Acetaldehyde