Brandl, Katharina and Sun, Lei and Neppl, Christina and Siggs, Owen M. and Le Gall, Sylvain M. and Tomisato, Wataru and Li, Xiaohong and Du, Xin and Maennel, Daniela N. and Blobel, Carl P. and Beutler, Bruce (2010) MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107 (46). pp. 19967-19972. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Toll-like receptors (TLRs) trigger intestinal inflammation when the epithelial barrier is breached by physical trauma or pathogenic microbes. Although it has been shown that TLR-mediated signals are ultimately protective in models of acute intestinal inflammation [such as dextran sulfate sodium (DSS)-induced colitis], it is less clear which cells mediate protection. Here we demonstrate that TLR signaling in the nonhematopoietic compartment confers protection in acute DSS-induced colitis. Epithelial cells of MyD88/Trif-deficient mice express diminished levels of the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG), and systemic lipopolysaccharide administration induces their expression in the colon. N-ethyl-N-nitrosourea (ENU)-induced mutations in Adam17 (which is required for AREG and EREG processing) and in Egfr both produce a strong DSS colitis phenotype, and the Adam17 mutation exerts its deleterious effect in the nonhematopoietic compartment. The effect of abrogation of TLR signaling is mitigated by systemic administration of AREG. A TLR-->MyD88-->AREG/EREG-->EGFR signaling pathway is represented in nonhematopoietic cells of the intestinal tract, responds to microbial stimuli once barriers are breached, and mediates protection against DSS-induced colitis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTOR-4; CHRONIC INTESTINAL INFLAMMATION; SULFATE-INDUCED COLITIS; INCREASED SUSCEPTIBILITY; INNATE IMMUNITY; CROHNS-DISEASE; MUTATION; INJURY; ALPHA; epidermal growth factor receptor signaling; inflammatory bowel disease; Toll-like receptor signaling; ENU mutagenesis; intestinal homeostasis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2020 12:10 |
| Last Modified: | 06 Jul 2020 12:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23879 |
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