Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells.
We investigated the effect of several amino acids on the secretion of such inflammatory cytokines as interleukin-8 (IL-8) induced by hydrogen peroxide or tumor necrosis factor-alpha (TNF-alpha) in intestinal epithelial-like Caco-2 and HT-29 cells. We found that histidine, one of the conditionally essential amino acids, significantly inhibited both hydrogen peroxide- and TNF-alpha-induced IL-8 secretion and mRNA expression in Caco-2 cells and HT-29 cells. These inhibitions were dose dependent and the inhibition rate of hydrogen peroxide-induced IL-8 secretion reached more than 50% at a concentration of 25mM, with over 95% inhibition at a concentration of 50mM. TNF-alpha increased the transcriptional activity of the IL-8 promoter which was significantly inhibited by treating Caco-2 cells with histidine. Histidine also abolished the NF-kappaB-dependent activation of the IL-8 promoter induced by TNF-alpha. These results indicate that histidine inhibited the hydrogen peroxide- and TNF-alpha-induced IL-8 secretion at the transcriptional level in intestinal epithelial cells, suggesting that histidine has the potential to attenuate intestinal inflammation.
Son
Dong Ok
DO
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. aa57027@mail.ecc.u-tokyo.ac.jp
Satsu
Hideo
H
Shimizu
Makoto
M
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016209:Interleukin-8; D016328:NF-kappa B; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D006639:Histidine; D006861:Hydrogen Peroxide