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

Nuclear factor-kappa B (NF-κB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-κB is sequestered in the cytoplasm by inhibitory IκB proteins. Extracellular stimuli, notably interleukin-1β (IL-1β) and tumor necrosis factorα (TNF-α) activate NF-κB nuclear translocation via IκB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects of butyrate on NF-κB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose-dependent inhibition of IL-1β-mediated NF-κB nuclear translocation was observed. However, IκBα phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1β-induced NF-κB activation by butyrate does not require an intact IκBα protein.