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 IkappaB proteins. Extracellular stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB 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-1beta-mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB alpha protein.
Lührs
H
H
Department of Medicine, University of Würzburg, Germany.
Gerke
T
T
Boxberger
F
F
Backhaus
K
K
Melcher
R
R
Scheppach
W
W
Menzel
T
T
D002087:Butyrates / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D014178:Translocation, Genetic / Q000187:drug effects*
D002087:Butyrates; D007375:Interleukin-1; D016328:NF-kappa B