MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice
| Autor: | Luke A. J. O'Neill, Gabriella Aviello, Padraic G. Fallon, Daniel G.W. Johnston, Sinéad C. Corr |
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| Přispěvatelé: | Aviello, G., Corr, S. C., Johnston, D. G. W., O'Neill, L. A. J., Fallon, P. G. |
| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Physiology Colorectal cancer Colorectal Neoplasm Severity of Illness Index chemistry.chemical_compound Mice Homeostasis Receptor Bone Marrow Transplantation Mice Knockout Caco-2 Cell Membrane Glycoproteins Dextran Sulfate Gastroenterology Colitis Colon cancer Female Membrane Glycoprotein medicine.symptom Colorectal Neoplasms Human Time Factor Colon Azoxymethane Inflammation Biology Bone marrow chimera Physiology (medical) Goll-like receptor Homeostasi medicine Animals Humans Transplantation Chimera Hepatology Animal Receptors Interleukin-1 medicine.disease MyD88 Mice Inbred C57BL Membrane glycoproteins Disease Models Animal chemistry Caco-2 biology.protein Cancer research Caco-2 Cells Coliti |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 306(9) |
| ISSN: | 1522-1547 |
| Popis: | Toll-like receptors (TLRs) play a central role in the recognition and response to microbial pathogens and in the maintenance and function of the epithelial barrier integrity in the gut. The protein MyD88 adaptor-like (Mal/TIRAP) serves as a bridge between TLR2/TLR4- and MyD88-mediated signaling to orchestrate downstream inflammatory responses. Whereas MyD88 has an essential function in the maintenance of intestinal homeostasis, a role for Mal in this context is less well described. Colitis was induced in wild-type (WT) and Mal-deficient ( Mal −/−) mice by administration of dextran sodium sulfate (DSS). Colitis-associated cancer was induced by DSS and azoxymethane (AOM) treatment. Chimeric mice were generated by total body gamma irradiation followed by transplantation of bone marrow cells. In the DSS model of colon epithelial injury, Mal −/− mice developed increased inflammation and severity of colitis relative to WT mice. Mal −/− mice demonstrated the presence of inflammatory cell infiltrates, increased crypt proliferation, and presence of neoformations. Furthermore, in the AOM/DSS model, Mal −/− mice had greater incidence of tumors. Mal −/− and WT bone marrow chimeras demonstrated that nonhematopoietic cell expression of Mal had an important protective role in the control of intestinal inflammation and inflammation-associated cancer. Mal is essential for the maintenance of intestinal homeostasis and expression of Mal in nonhematopoietic cells prevents chronic intestinal inflammation that may predispose to colon neoplasia. |
| Databáze: | OpenAIRE |
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