Acetaldehyde inhibits NF-κB activation through IκBα preservation in rat Kupffer cells

Background and aims. Treatment with acetaldehyde dehydrogenase inhibitors leads to increased liver acetaldehyde levels and prevents hepatic inflammation 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 effect on degradation of I kappa B alpha and activation of NF-kappa B in LPS-stimulated rat Kupffer cells. Methods. Kupffer cells were isolated from male Sprague-Dawley rats and preincubated with various concentrations of acetaldehyde (25-100 mu M). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. I epsilon B alpha and p65 proteins and activation of NF-kappa B were evaluated. Results. In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of I kappa B alpha, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-kappa B activation. Conclusions. Acetaldehyde is clearly involved in the stabilization of I kappa B alpha protein and suppression of NF-kappa B activation in rat Kupffer cells. Acetaldehyde may form an adduct with I kappa B alpha, thus making the protein less susceptible to degradation. (C) 1998 Academic Press.