title: Bovine glycomacropeptide has intestinal antiinflammatory effects in rats with dextran sulfate-induced colitis.
abstract: Milk κ-casein-derived bovine glycomacropeptide (GMP) has immunomodulatory and bacterial toxin-binding effects, and it has been shown to exert intestinal antiinflammatory activity in the trinitrobenzenesulfonic acid-induced model of colitis. However, its mechanism of action is not well characterized, and it is not known whether GMP is effective in other experimental models. The intestinal antiinflammatory activity of GMP was assessed in the dextran sulfate sodium (DSS)-induced model of rat colitis. DSS was applied at a starting concentration of 5% (wt:v) in drinking water and adjusted when the disease activity index (DAI) increased substantially for 10 d. There were 3 experimental groups: control (no inflammation), DSS, and GMP (GMP-treated rats with DSS-induced colitis). GMP pretreatment (500 mg · kg(-1) · d(-1), starting 2 d before DSS treatment) reduced the DAI by 60% and lowered the colonic damage score by 44% (P < 0.05). GMP fully normalized the colonic expression of interleukin (IL) 1β, IL17, IL23, IL6, transforming growth factor β, IL10, and Foxp3 as assessed by quantitative RT-PCR. The production of interferon-γ by mesenteric lymph node cells ex vivo was also normalized by GMP treatment. In contrast, GMP did not change colonic thickening, myeloperoxidase, cyclooxygenase 2, or alkaline phosphatase. Histology analysis showed better preservation of the epithelium and attenuated infiltration and submucosal thickening in rats treated with GMP. We conclude that GMP exerts intestinal antiinflammatory activity in this model, which may be primarily related to actions on Th1 and Th17 lymphocytes and perhaps macrophages.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Granada 18071, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: López-Posadas
authors.forename: Pilar
authors.initials: P
authors.lastname: Requena
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Suárez
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Fermín
authors.initials: F
authors.lastname: Sánchez de Medina
authors.forename: Olga
authors.initials: O
authors.lastname: Martínez-Augustin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use*; D002364:Caseins / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000503:physiopathology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002364:Caseins; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D006020:Glycopeptides; D018836:Inflammation Mediators; D012333:RNA, Messenger; C020251:kappa-casein glycomacropeptide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat