Acetaldehyde inhibits NF-kappaB activation through IkappaBalpha preservation in rat Kupffer cells

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 IkappaBa preservation and decreased activation of nuclear factor (NF)-kappaB. The present in vitro study was aimed to clarify whether acetaldehyde has an effect on degradation of IkappaBalpha and activation of NF-kappaB in LPS-stimulated rat Kupffer cells.

Kupffer cells were isolated from male Sprague-Dawley rats and preincubated with various concentrations of acetaldehyde (25-100 microM). Thereafter the cells were stimulated with LPS, and cytosolic and nuclear fractions were prepared. IkappaBalpha and p65 proteins and activation of NF-kappaB were evaluated.

In LPS-stimulated rat Kupffer cells, acetaldehyde diminished proteolytic degradation of IkappaBalpha, inhibited nuclear translocation of cytosolic p65 protein, and, accordingly, markedly decreased NF-kappaB activation.

Acetaldehyde is clearly involved in the stabilization of IkappaBalpha protein and suppression of NF-kappaB activation in rat Kupffer cells. Acetaldehyde may form an adduct with IkappaBalpha, thus making the protein less susceptible to degradation.