Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis.
Milk κ-casein-derived bovine glycomacropeptide (GMP) exerts immunomodulatory effects. It exhibits intestinal anti-inflammatory activity in chemically induced models of colitis. However, to validate its clinical usefulness as a nutraceutical, it is important to assess its effects in a model with a closer pathophysiological connection with human inflammatory bowel disease. Therefore, in the present study, we used the lymphocyte-transfer model of colitis in mice and compared the effects of GMP in this model with those obtained in the dextran sulphate sodium (DSS) model. GMP (15 mg/d) resulted in higher body-weight gain and a reduction of the colonic damage score and myeloperoxidase (MPO) activity in Rag1(-/-) mice with colitis induced by the transfer of naïve T cells. The colonic and ileal weight:length ratio was decreased by approximately 25%, albeit non-significantly. GMP treatment reduced the percentage of CD4⁺ interferon (IFN)-γ⁺ cells in mesenteric lymph nodes (MLN). The basal production of IL-6 by MLN obtained from the GMP-treated mice ex vivo was augmented. However, concanavalin A-evoked production was similar. The colonic expression of regenerating islet-derived protein 3γ, S100A8, chemokine (C-X-C motif) ligand 1 and IL-1β was unaffected by GMP, while that of TNF-α and especially IFN-γ was paradoxically increased. In the DSS model, GMP also reduced the activity of colonic MPO, but it failed to alter weight gain or intestinal weight:length ratio. GMP augmented the production of IL-10 by MLN cells and was neutral towards other cytokines, except exhibiting a trend towards increasing the production of IL-6. The lower effect was attributed to the lack of the effect of GMP on epithelial cells. In conclusion, GMP exerts intestinal anti-inflammatory effects in lymphocyte-driven colitis.
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Mercedes
M
Ortega-González
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Fermín
F
Capitán-Cañadas
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Pilar
P
Requena
Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Borja
B
Ocón
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Isabel
I
Romero-Calvo
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Carlos
C
Aranda
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
María Dolores
MD
Suárez
Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Antonio
A
Zarzuelo
Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Fermín
F
Sánchez de Medina
Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Olga
O
Martínez-Augustin
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002364:Caseins / Q000627:therapeutic use*; D002417:Cattle; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008640:Mesenteric Lymphadenitis / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D010446:Peptide Fragments / Q000627:therapeutic use*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D011897:Random Allocation; D015430:Weight Gain
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D002364:Caseins; D005765:Gastrointestinal Agents; D018398:Homeodomain Proteins; D010446:Peptide Fragments; C065989:caseinomacropeptide; C064658:RAG-1 protein; D009195:Peroxidase