title: 5-caffeoylquinic acid and caffeic acid down-regulate the oxidative stress- and TNF-alpha-induced secretion of interleukin-8 from Caco-2 cells.
abstract: Although chlorogenic acid (CHA) easily reaches a millimolar level in the gastrointestinal tract because of its high concentration in coffee and fruits, its effects on intestinal epithelial cells have been little reported. We investigated in this study the down-regulative effects of 5-caffeoylquinic acid (CQA), the predominant isomer of CHA, on the H(2)O(2-) or TNF-alpha-induced secretion of interleukin (IL)-8, a central pro-inflammatory chemokine involved in the pathogenesis of inflammatory bowel diseases, in human intestinal epithelial Caco-2 cells. After the cells had been pre- and simultaneously treated with CQA, the oversecretion of IL-8 and overexpression of its mRNA induced by H(2)O(2) were significantly suppressed in a dose-dependent manner in the range of 0.25-2.00 mmol/L. We further found that a metabolite of CQA, caffeic acid (CA), but not quinic acid, significantly inhibited the H(2)O(2)-induced IL-8 secretion and its mRNA expression in the same dose-dependent manner. Both CQA and CA suppressed the TNF-alpha-induced IL-8 secretion as well. Caffeic acid at 2.00 mmol/l was able to absolutely block the H(2)O(2)- or TNF-alpha-induced oversecretion of IL-8 in Caco-2 cells. However, CQA and CA did not suppress the TNF-alpha-induced increase in the IL-8 mRNA expression, indicating that the suppressive mechanisms are different between TNF-alpha-induced and H(2)O(2)-induced IL-8 production models. These results suggest that the habit of drinking coffee and/or eating fruits with a high CHA content may be beneficial to humans in preventing the genesis of inflammatory bowel diseases.
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. zhaohuizhao@hotmail.com
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Hee Soon
authors.initials: HS
authors.lastname: Shin
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Totsuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D018938:Caco-2 Cells; D002109:Caffeic Acids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002109:Caffeic Acids; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C472707:caffeoylquinic acid; D011801:Quinic Acid; D006861:Hydrogen Peroxide; C040048:caffeic acid