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

Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-kappaB is sequestered in the cytoplasm by inhibitory I kappaB proteins. Extracellular stimuli, notably interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via I kappaB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects 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 translocation was observed. However, I kappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1 beta -induced NF-kappaB activation by butyrate does not require an intact I kappaB alpha protein.