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β-Casein(94-123)-derived peptides differently modulate production of mucins in intestinal goblet cells

Published online by Cambridge University Press:  22 October 2014

Pascale Plaisancié*
Affiliation:
INRA USC1235, INSERM U1060, CarMeN Laboratory, University Lyon-1, INSA-Lyon, IMBL, Bât. Louis Pasteur, 20 av. Albert Einstein, 69621, F-69100 Villeurbanne, France
Rachel Boutrou
Affiliation:
INRA, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France AGROCAMPUS OUEST, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France
Monique Estienne
Affiliation:
INRA USC1235, INSERM U1060, CarMeN Laboratory, University Lyon-1, INSA-Lyon, IMBL, Bât. Louis Pasteur, 20 av. Albert Einstein, 69621, F-69100 Villeurbanne, France
Gwénaële Henry
Affiliation:
INRA, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France AGROCAMPUS OUEST, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France
Julien Jardin
Affiliation:
INRA, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France AGROCAMPUS OUEST, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France
Armelle Paquet
Affiliation:
INRA USC1235, INSERM U1060, CarMeN Laboratory, University Lyon-1, INSA-Lyon, IMBL, Bât. Louis Pasteur, 20 av. Albert Einstein, 69621, F-69100 Villeurbanne, France
Joëlle Léonil
Affiliation:
INRA, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France AGROCAMPUS OUEST, UMR1253 Science et Technologie du Lait et de l'Œuf, F-35000 Rennes, France
*
*For correspondence; e-mail: pascale.plaisancie@inserm.fr

Abstract

We recently reported the identification of a peptide from yoghurts with promising potential for intestinal health: the sequence (94-123) of bovine β-casein. This peptide, composed of 30 amino acid residues, maintains intestinal homoeostasis through production of the secreted mucin MUC2 and of the transmembrane-associated mucin MUC4. Our study aimed to search for the minimal sequence responsible for the biological activity of β-CN(94-123) by using several strategies based on (i) known bioactive peptides encrypted in β-CN(94-123), (ii) in silico prediction of peptides reactivity and (iii) digestion of β-CN(94-123) by enzymes of intestinal brush border membranes. The revealed sequences were tested in vitro on human intestinal mucus-producing HT29-MTX cells. We demonstrated that β-CN(108-113) (an ACE-inhibitory peptide) and β-CN(114-119) (an opioid peptide named neocasomorphin-6) up-regulated MUC4 expression whereas levels of the secreted mucins MUC2 and MUC5AC remained unchanged. The digestion of β-CN(94-123) by intestinal enzymes showed that the peptides β-CN(94-108) and β-CN(117-123) were present throughout 1·5 to 3 h of digestion, respectively. These two peptides raised MUC5AC expression while β-CN(117-123) also induced a decrease in the level of MUC2 mRNA and protein. In addition, this inhibitory effect was reproduced in airway epithelial cells. In conclusion, β-CN(94-123) is a multifunctional molecule but only the sequence of 30 amino acids has a stimulating effect on the production of MUC2, a crucial factor of intestinal protection.

Type
Research Article
Copyright
Copyright © Proprietors of Journal of Dairy Research 2014 

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References

Borchers, MT, Carty, MP & Leikauf, GD 1999 Regulation of human airway mucins by acrolein and inflammatory mediators. American Journal of Physiology 276 L549L555Google Scholar
Boutrou, R, Jardin, J, Blais, A, Tome, D & Leonil, J 2008 Glycosylations of kappa-casein-derived caseinomacropeptide reduce its accessibility to endo- but not exointestinal brush border membrane peptidases. Journal of Agricultural and Food Chemistry 56 81668173. doi: 10.1021/jf801140dCrossRefGoogle Scholar
Boutrou, R, Gaudichon, C, Dupont, D, Jardin, J, Airinei, G, Marsset-Baglieri, A, Benamouzig, R, Tome, D & Leonil, J 2013 Sequential release of milk protein-derived bioactive peptides in the jejunum in healthy humans. American Journal of Clinical Nutrition 97 13141323Google Scholar
Corazziari, ES 2009 Intestinal mucus barrier in normal and inflamed colon. Journal of Pediatric Gastroenterology and Nutrition 48(Suppl. 2)S54S55Google Scholar
Corfield, AP 2014 Mucins: a biologically relevant glycan barrier in mucosal protection. Biochimica et Biophysica acta. doi: 10.1016/j.bbagen.2014.05.003Google Scholar
Corfield, AP, Myerscough, N, Longman, R, Sylvester, P, Arul, S & Pignatelli, M 2000 Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease. Gut 47 589594Google Scholar
Corfield, AP, Carroll, D, Myerscough, N & Probert, CS 2001 Mucins in the gastrointestinal tract in health and disease. Frontiers in Bioscience 6 D1321D1357CrossRefGoogle ScholarPubMed
El Homsi, M, Ducroc, R, Claustre, J, Jourdan, G, Gertler, A, Estienne, M, Bado, A, Scoazec, JY & Plaisancie, P 2007 Leptin modulates the expression of secreted and membrane-associated mucins in colonic epithelial cells by targeting PKC, PI3K, and MAPK pathways. American Journal of Physiology Gastrointestinal and Liver Physiology 293 G365G373CrossRefGoogle ScholarPubMed
Gaudier, E, Jarry, A, Blottiere, HM, de Coppet, P, Buisine, MP, Aubert, JP, Laboisse, C, Cherbut, C & Hoebler, C 2004 Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. American Journal of Physiology Gastrointestinal and Liver Physiology 287 G1168G1174Google Scholar
Gosalia, N, Leir, SH & Harris, A 2013 Coordinate regulation of the gel forming mucin genes at chromosome 11p15.5. Journal of Biological Chemistry 288 67176725Google Scholar
Gum, JR Jr, Hicks, JW, Gillespie, AM, Carlson, EJ, Komuves, L, Karnik, S, Hong, JC, Epstein, CJ & Kim, YS 1999 Goblet cell-specific expression mediated by the MUC2 mucin gene promoter in the intestine of transgenic mice. American Journal of Physiology Gastrointestinal and Liver Physiology 276 G666G676Google Scholar
Gupta, A, Mann, B, Kumar, R & Ram Bhagat, S 2010 Identification of antioxidant peptides in cheddar cheese made with adjunct culture Lactobacillus casei ssp. casei 300. Milchwissenschaft 65 396399Google Scholar
Habte, HH, Kotwal, GJ, Lotz, ZE, Tyler, MG, Abrahams, M, Rodriques, J, Kahn, D & Mall, AS 2007 Antiviral activity of purified human breast milk mucin. Neonatology 92 96104CrossRefGoogle ScholarPubMed
Habte, HH, de Beer, C, Lotz, ZE, Tyler, MG, Kahn, D & Mall, AS 2008 Inhibition of human immunodeficiency virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology 93 162170Google Scholar
Han, SY, Lee, MS, Kim, HR, Baek, SH, Ahn, DH, Chae, HS, Erickson, RH, Sleisenger, MH & Kim, YS 2000 Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. International Journal of Clinical Oncology 17 487494Google Scholar
Jinsmaa, Y & Yoshikawa, M 1999 Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein. Peptides 20 957962Google Scholar
Kai, H, Yoshitake, K, Hisatsune, A, Kido, T, Isohama, Y, Takahama, K & Miyata, T 1996 Dexamethasone suppresses mucus production and MUC-2 and MUC-5AC gene expression by NCI-H292 cells. American Journal of Physiology 271 L484L488Google Scholar
Li, JD, Dohrman, AF, Gallup, M, Miyata, S, Gum, JR, Kim, YS, Nadel, JA, Prince, A & Basbaum, CB 1997 Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proceedings of the National Academy of Sciences of the United States of America 94 967972CrossRefGoogle ScholarPubMed
Liu, B, Yu, Z, Chen, C, Kling, DE & Newburg, DS 2012 Human milk mucin 1 and mucin 4 inhibit Salmonella enterica serovar Typhimurium invasion of human intestinal epithelial cells in vitro. Journal of Nutrition 142 15041509Google Scholar
Livak, KJ & Schmittgen, TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 402408Google Scholar
Martinez-Maqueda, D, Miralles, B, De Pascual-Teresa, S, Reveron, I, Munoz, R & Recio, I 2012 Food-derived peptides stimulate mucin secretion and gene expression in intestinal cells. Journal of Agricultural and Food Chemistry 60 86008605Google Scholar
Mizoshita, T, Tsukamoto, T, Inada, KI, Hirano, N, Tajika, M, Nakamura, T, Ban, H & Tatematsu, M 2007 Loss of MUC2 expression correlates with progression along the adenoma-carcinoma sequence pathway as well as de novo carcinogenesis in the colon. Histology and Histopathology 22 251260Google Scholar
Mudter, J 2011 From intestinal stem cells to inflammatory bowel diseases. World Journal of Gastroenterology 17 31983203Google Scholar
Pelaseyed, T, Bergstrom, JH, Gustafsson, JK, Ermund, A, Birchenough, GM, Schutte, A, van der Post, S, Svensson, F, Rodriguez-Pineiro, AM, Nystrom, EE, Wising, C, Johansson, ME & Hansson, GC 2014 The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunological Reviews 260 820Google Scholar
Pfaffl, MW, Horgan, GW & Dempfle, L 2002 Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 30 e36CrossRefGoogle Scholar
Philanto-Leppälä, A, Rokka, T & Korhonen, H 1998 Angiotensin I converting enzyme inhibitory peptides derived from bovine milk proteins. International Dairy Journal 8 325331Google Scholar
Plaisancie, P, Claustre, J, Estienne, M, Henry, G, Boutrou, R, Paquet, A & Leonil, J 2013 A novel bioactive peptide from yoghurts modulates expression of the gel-forming MUC2 mucin as well as population of goblet cells and Paneth cells along the small intestine. Journal of Nutritional Biochemistry 24 213221Google Scholar
Pugh, S, Jayaraj, AP & Bardhan, KD 1996 Duodenal mucosal histology and histochemistry in active, treated and healed duodenal ulcer: correlation with duodenal prostaglandin E2 production. Journal of Gastroenterology and Hepatology 11 120124Google Scholar
Rose, MC, Piazza, FM, Chen, YA, Alimam, MZ, Bautista, MV, Letwin, N & Rajput, B 2000 Model systems for investigating mucin gene expression in airway diseases. Journal of Aerosol Medicine 13 245261Google Scholar
Ruvoen-Clouet, N, Mas, E, Marionneau, S, Guillon, P, Lombardo, D & Le Pendu, J 2006 Bile-salt-stimulated lipase and mucins from milk of ‘secretor’ mothers inhibit the binding of Norwalk virus capsids to their carbohydrate ligands. Biochemical Journal 393 627634CrossRefGoogle ScholarPubMed
Strugala, V, Dettmar, PW & Pearson, JP 2008 Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn's disease. International Journal of Clinical Practice 62 762769Google Scholar
Sylvester, PA, Myerscough, N, Warren, BF, Carlstedt, I, Corfield, AP, Durdey, P & Thomas, MG 2001 Differential expression of the chromosome 11 mucin genes in colorectal cancer. Journal of Pathology 195 327335Google Scholar
Teschemacher, H 2003 Opioid receptor ligands derived from food proteins. Current Pharmaceutical Design 9 13311344Google Scholar
Van der Sluis, M, De Koning, BA, De Bruijn, AC, Velcich, A, Meijerink, JP, Van Goudoever, JB, Buller, HA, Dekker, J, Van Seuningen, I, Renes, IB & Einerhand, AW 2006 Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131 117129Google Scholar
Velcich, A, Yang, W, Heyer, J, Fragale, A, Nicholas, C, Viani, S, Kucherlapati, R, Lipkin, M, Yang, K & Augenlicht, L 2002 Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295 17261729Google Scholar
Voynow, JA, Gendler, SJ & Rose, MC 2006 Regulation of mucin genes in chronic inflammatory airway diseases. American Journal of Respiratory Cell and Molecular Biology 34 661665Google Scholar
Zoghbi, S, Trompette, A, Claustre, J, El Homsi, M, Garzon, J, Jourdan, G, Scoazec, JY & Plaisancie, P 2006 beta-Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a mu-opioid pathway. American Journal of Physiology Gastrointestinal and Liver Physiology 290 G1105G1113Google Scholar
Zoghbi, S, Drouin, E, Claustre, J, Bara, J, Scoazec, JY & Plaisancie, P 2007 Intestinal MUC2 and gastric M1/MUC5AC in preneoplastic lesions induced by 1,2-dimethylhydrazine in rat: a sequential analysis. International Journal of Oncology 30 489497Google Scholar