title: Sulfation of colonic mucins by N-acetylglucosamine 6-O-sulfotransferase-2 and its protective function in experimental colitis in mice.
abstract: N-Acetylglucosamine 6-O-sulfotransferase-2 (GlcNAc6ST-2) catalyzes the sulfation of mucin-like glycoproteins, which function as ligands for a lymphocyte homing receptor, L-selectin, in the lymph node high endothelial venules (HEVs). We previously showed that GlcNAc6ST-2 is expressed not only in lymph node HEVs but also in the colonic epithelial cells in mice. Here we investigated the regulatory mechanism and physiological significance of colonic expression of GlcNAc6ST-2 in mice. Treatment of a mouse colonic epithelial cell line with butyrate, a short-chain fatty acid produced by anaerobic bacteria, induced GlcNAc6ST-2 expression in the presence of epidermal growth factor. Administration of butyrate in the drinking water stimulated GlcNAc6ST-2 expression in the mouse intestine, indicating that butyrate could serve as a regulatory molecule for the GlcNAc6ST-2 expression in vivo. Immunohistochemical analysis indicated that the sulfation of colonic mucins was greatly diminished in GlcNAc6ST-2-deficient mice. Liquid chromatography coupled to electrospray ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type and GlcNAc6ST-2-deficient mice showed that GlcNAc-6-O-sulfation was the predominant sulfate modification of these mucins, and it was exclusively mediated by GlcNAc6ST-2. After colitis induction by dextran sulfate sodium, significantly more leukocyte infiltration was observed in the colon of GlcNAc6ST-2-deficient mice than in that of wild-type mice, indicating that the sulfation of colonic mucins by GlcNAc6ST-2 has a protective function in experimental colitis. These findings indicate that GlcNAc6ST-2, whose expression is regulated by butyrate, is a major sulfotransferase in the biosynthesis of sulfomucins in the mouse colon, where they serve as a mucosal barrier against colonic inflammation.
authors.affiliation: Laboratory of Microbiology and Immunology and the Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tobisawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D003092:Colitis / Q000201:enzymology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D009077:Mucins / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D002087:Butyrates; D009077:Mucins; D013431:Sulfates; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases