Alcohol and alcoholism : international journal of the Medical Council on Alcoholism
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Comparative Study
Effects of acetaldehyde and TNF alpha on the inhibitory kappa B-alpha protein and nuclear factor kappa B activation in hepatic stellate cells.
Increased plasma tumour necrosis alpha (TNFalpha) and elevated monocyte nuclear factor kappa B (NF-kappaB) are associated with liver injury and inflammation in models of alcoholic liver disease and are found to be elevated in monocytes of patients with alcoholic hepatitis. Acetaldehyde enhances, whereas TNFalpha inhibits, transcription of the type I collagen promoters and type I collagen production. NF-kappaB, an inhibitor of the type I collagen promoters, is increased by both acetaldehyde and TNFalpha. This study determined the effects of acetaldehyde in comparison to the effects of TNFalpha on inhibitory kappa B-alpha (IkappaB-alpha) protein and NF-kappaB activation in hepatic stellate cells. ⋯ TNFalpha and acetaldehyde independently activate NF-kappaB by rapid enhancement of IkappaB-alpha kinase activity and degradation of IkB-alpha protein. Increased TNFalpha is the principal mechanism for the elevation of NF-kappaB in severe alcoholic hepatitis. The elevation of NF-kappaB due to TNFalpha enhance liver injury, but inhibit fibrogenesis. In contrast, the effect of acetaldehyde in activating NF-kappaB is associated with increases in both liver injury and fibrogenesis, indicating that the effects of acetaldehyde on fibrogenesis are mediated by cytokines and by trans-acting factors other than NF-kappaB.
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To investigate glutamate receptor subtypes during alcohol withdrawal. ⋯ NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal.