title: Interleukin 10-deficient mice exhibit defective colonic Muc2 synthesis before and after induction of colitis by commensal bacteria.
abstract: Germ-free (GF) interleukin 10-deficient (IL-10) mice develop chronic colitis after colonization by normal enteric bacteria. Muc2 is the major structural component of the protective colonic mucus. Our aim was to determine whether primary or induced aberrations in Muc2 synthesis occur in GF IL-10 mice that develop colitis after bacterial colonization. GF IL-10 and wild-type mice were colonized with commensal bacteria for various intervals up to 6 weeks. Colitis was quantified by histologic score and IL-12 secretion. Muc2 synthesis, total level of Muc2, and Muc2 sulfation were measured quantitatively. GF IL-10 mice showed 10-fold lower Muc2 synthesis and Muc2 levels compared with GF wild-type mice, but Muc2 sulfation was not different. When bacteria were introduced, IL-10 mice developed colitis, whereas wild-type mice remained healthy. Muc2 synthesis was unchanged in wild-type mice, but IL-10 mice showed a peak increase in Muc2 synthesis 1 week after bacterial introduction, returning to baseline levels after 2 weeks. Total Muc2 levels decreased 2-fold in wild-type mice but remained at stable low levels in IL-10 mice. Upon introducing bacteria, Muc2 sulfation increased 2-fold in wild-type mice, whereas in IL-10 mice Muc2 sulfation decreased 10-fold. In conclusion, a primary defect in colonic Muc2 synthesis is present in IL-10 mice, whereas bacterial colonization and colitis in these mice led to reduced Muc2 sulfation. These quantitative and structural aberrations in Muc2 in IL-10 mice likely reduce the ability of their mucosa to cope with nonpathogenic commensal bacteria and may contribute to their susceptibility to develop colitis.
authors.affiliation: Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Nicole M J
authors.initials: NM
authors.lastname: Schwerbrock
authors.forename: Mireille K
authors.initials: MK
authors.lastname: Makkink
authors.forename: Maria
authors.initials: M
authors.lastname: van der Sluis
authors.forename: Hans A
authors.initials: HA
authors.lastname: Büller
authors.forename: Alexandra W C
authors.initials: AW
authors.lastname: Einerhand
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Jan
authors.initials: J
authors.lastname: Dekker
mesh_terms: D000818:Animals; D001419:Bacteria / Q000472:pathogenicity; D015152:Blotting, Northern; D003093:Colitis, Ulcerative / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D000071165:Trefoil Factor-3
chemical_list: C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3; D016753:Interleukin-10