title: The Anti-atherosclerotic Dipeptide, Trp-His, Reduces Intestinal Inflammation through the Blockade of L-Type Ca2+ Channels.
abstract: Trp-His, the anti-atherosclerotic dipeptide, exerted an antiproliferative effect on vascular smooth muscle cells by L-type Ca(2+) channel blocker-like effect. The beneficial potential by the blockade of Ca(2+) channels on chronic intestinal inflammation, including inflammatory bowel disease (IBD), is unclear. Trp-His (100 or 250 mg/kg body weight/day) was administered for 14 days to BALB/c mice, and 5% dextran sodium sulfate (DSS) was administered to induce colitis in the last 7 days. Trp-His reduced DSS-induced typical colitis symptoms and cytokine expression in the colon. Trp-His inhibited interleukin (IL)-8 secretion in tumor necrosis factor (TNF)-α-stimulated HT-29 cells. The inhibitory effect of Trp-His, as well as that of Ca(2+) channel blockers, was impaired by the presence of Ca(2+) channel agonist Bay K 8644. The TNF-α-induced activation of mitogen-activated protein kinases (MAPKs) and IκBα were decreased by Trp-His. These results indicated that the anti-inflammatory effect of Trp-His may be involved in the blockade of L-type Ca(2+) channels.
authors.affiliation: †Department of Food Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada.|§Division of Bioresources and Bioenvironmental Sciences, Faculty of Agriculture, Graduate School, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: †Department of Food Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kovacs-Nolan
authors.affiliation: §Division of Bioresources and Bioenvironmental Sciences, Faculty of Agriculture, Graduate School, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
authors.affiliation: †Department of Food Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mine
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000276:immunology*; D004151:Dipeptides / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D020746:Calcium Channels, L-Type; D004151:Dipeptides; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C509582:tryptophyl-histidine
keywords: L-type Ca2+ channels; Trp-His; dextran sodium sulfate; dipeptide; inflammatory bowel disease; intestinal epithelial cell