Butyrate inhibits interleukin-1-mediated nuclear factor-kappa B activationin human epithelial cells

Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for t he inducible expression of multiple genes involved in inflammation. NF-kapp aB is sequestered in the cytoplasm by inhibitory I kappaB proteins. Extrace llular stimuli, notably interleukin-1 beta (IL-1 beta) and tumor necrosis f actor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via I kapp aB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effec ts of butyrate on NF-kappaB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose -dependent inhibition of IL-1 beta -mediated NF-kappaB nuclear translocatio n was observed. However, I kappaB alpha phosphorylation and degradation occ urred rapidly in both butyrate pretreated and nonpretreated cells, respecti vely. These data indicate that inhibition of IL-1 beta -induced NF-kappaB a ctivation by butyrate does not require an intact I kappaB alpha protein.