Acetaldehyde inhibits NF-kappa B activation through I kappa B alpha preservation in rat Kupffer cells

Background and aims. Treatment with acetaldehyde dehydrogenase inhibitors l eads to increased liver acetaldehyde levels and prevents hepatic inflammati on and necrosis in ethanol-fed rats. This is accompanied by I kappa B alpha preservation and decreased activation of nuclear factor (NF)-kappa B. The present in vitro study was aimed to clarify whether acetaldehyde has an eff ect on degradation of I kappa B alpha and activation of NF-kappa B in LPS-s timulated rat Kupffer cells. Methods. Kupffer cells were isolated from male Sprague-Dawley rats and preincubated with various concentrations of acetal dehyde (25-100 mu M). Thereafter the cells were stimulated with LPS, and cy tosolic and nuclear fractions were prepared. I epsilon B alpha and p65 prot eins and activation of NF-kappa B were evaluated. Results. In LPS-stimulate d rat Kupffer cells, acetaldehyde diminished proteolytic degradation of I k appa B alpha, inhibited nuclear translocation of cytosolic p65 protein, and , accordingly, markedly decreased NF-kappa B activation. Conclusions. Aceta ldehyde is clearly involved in the stabilization of I kappa B alpha protein and suppression of NF-kappa B activation in rat Kupffer cells. Acetaldehyd e may form an adduct with I kappa B alpha, thus making the protein less sus ceptible to degradation. (C) 1998 Academic Press.