Colitis development during the suckling-weaning transition in mucin Muc2-deficient mice
| Autor: | Maria van der Sluis, Nanda Burger-van Paassen, Günther Boehm, Peng Lu, Janneke Bouma, Anita M. Korteland-van Male, Isabelle Van Seuningen, Johannes B. van Goudoever, Ingrid B. Renes |
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| Přispěvatelé: | Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, General Paediatrics, Neonatology, Pediatrics, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Colon Physiology Cellular differentiation [SDV]Life Sciences [q-bio] Inflammation Weaning Biology digestive system Mice 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Colitis Growth Disorders 030304 developmental biology Mice Knockout Mucin-2 0303 health sciences Toll-like receptor Mucin-4 Hepatology Transition (genetics) Trefoil factor 3 Interleukins Mucin Mucins Gastroenterology Cell Differentiation respiratory system medicine.disease Toll-Like Receptor 2 digestive system diseases Interleukin-10 Endocrinology Myeloid Differentiation Factor 88 030211 gastroenterology & hepatology Goblet Cells Trefoil Factor-3 medicine.symptom |
| Zdroj: | AJP-Gastrointestinal and Liver Physiology AJP-Gastrointestinal and Liver Physiology, American Physiological Society, 2011, 301 (4), pp.G667-G678. ⟨10.1152/ajpgi.00199.2010⟩ American journal of physiology. Gastrointestinal and liver physiology, 301(4), G667-G678. American Physiological Society American Journal of Physiology-Gastrointestinal and Liver Physiology, 301, G667-G678. American Physiological Society AJP-Gastrointestinal and Liver Physiology, 2011, 301 (4), pp.G667-G678. ⟨10.1152/ajpgi.00199.2010⟩ |
| ISSN: | 0193-1857 1522-1547 |
| DOI: | 10.1152/ajpgi.00199.2010⟩ |
| Popis: | The mucin Muc2 is the structural component of the colonic mucus layer. Adult Muc2 knockout (Muc2−/−) mice suffer from severe colitis. We hypothesized that Muc2 deficiency induces inflammation before weaning of mother's milk [ postnatal day (P) 14] with aggravation of colitis after weaning (P28). Muc2−/−and wild-type mice were killed at embryonic day 18.5 and P1.5, P7.5, P14, P21, and P28. Colonic morphology, influx of T cells, and goblet cell-specific protein expression was investigated by (immuno)histochemistry. Cytokine and Toll-like receptor (TLR) profiles in the colon were analyzed by quantitative RT-PCR. Muc2−/−mice showed an increased and persistent influx of Cd3ε-positive T cells in the colonic mucosa as of P1.5. This was accompanied by mucosal damage at P28 in the distal colon but not in the proximal colon. At P14, the proinflammatory immune response [i.e., increased interleukin (IL)-12 p35, IL-12 p40, and tumor necrosis factor-α, expression] in the distal colon of Muc2−/−mice presented with an immune suppressive response [i.e., increased Foxp3, transforming growth factor (TGF)-β1, IL-10, and Ebi3 expression]. In contrast, at P28, a proinflammatory response remained in the distal colon, whereas the immune suppressive response (i.e., Foxp3 and TGF-β1 expression) declined. The proximal colon of Muc2−/−mice did not show morphological damage and was dominated by an immune suppressive response at P14 and P28. Interestingly, changes in expression of TLRs and TLR-related molecules were observed in the distal colon at P14 and P28 and in the proximal colon only at P28. Colitis in Muc2−/−mice is limited before weaning by immune suppressive responses and exacerbates in the distal colon after weaning because of the decline in the immune suppressive response. |
| Databáze: | OpenAIRE |
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