Interleukin 10-Deficient Mice Exhibit Defective Colonic Muc2 Synthesis Before and After Induction of Colitis by Commensal Bacteria
| Autor: | Alexandra W. C. Einerhand, Mireille K. Makkink, Nicole M.J. Schwerbrock, Maria van der Sluis, R. Balfour Sartor, Jan Dekker, Hans A. Büller |
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| Rok vydání: | 2004 |
| Předmět: |
Mucin 2
digestive system Microbiology Mice Sulfation medicine Animals Immunology and Allergy Secretion RNA Messenger Colitis Mice Knockout Mice Inbred BALB C Mucin-2 Bacteria biology Trefoil factor 3 Mucins Gastroenterology Interleukin respiratory system Blotting Northern biology.organism_classification medicine.disease digestive system diseases Interleukin-10 Specific Pathogen-Free Organisms Interleukin 10 Colitis Ulcerative Trefoil Factor-3 |
| Zdroj: | Inflammatory Bowel Diseases. 10:811-823 |
| ISSN: | 1078-0998 |
| DOI: | 10.1097/00054725-200411000-00016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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