title: Histidine inhibits oxidative stress- and TNF-alpha-induced interleukin-8 secretion in intestinal epithelial cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Dong Ok
authors.initials: DO
authors.lastname: Son
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: 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*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D006639:Histidine; D006861:Hydrogen Peroxide