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 IκBα preservation and decreased activation of nuclear factor (NF)-κB. The present in vitro study was aimed to clarify whether acetaldehyde has an effect on degradation of IκBα and activation of NF-κB 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 μM). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. IκBα and p65 proteins and activation of NF-κB were evaluated. Results. In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of IκBα, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-κB activation. Conclusions. Acetaldehyde is clearly involved in the stabilization of IκBα protein and suppression of NF-κB activation in rat Kupffer cells. Acetaldehyde may form an adduct with IκBα, thus making the protein less susceptible to degradation.