MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands.
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...
| Principais autores: | , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2010
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| _version_ | 1826292143932571648 |
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| author | Brandl, K Sun, L Neppl, C Siggs, O Le Gall, S Tomisato, W Li, X Du, X Maennel, D Blobel, C Beutler, B |
| author_facet | Brandl, K Sun, L Neppl, C Siggs, O Le Gall, S Tomisato, W Li, X Du, X Maennel, D Blobel, C Beutler, B |
| author_sort | Brandl, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:10:09Z |
| format | Journal article |
| id | oxford-uuid:b3eb4d2d-9e07-4d18-a4ad-2c025d473100 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:10:09Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:b3eb4d2d-9e07-4d18-a4ad-2c025d4731002022-03-27T04:22:31ZMyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b3eb4d2d-9e07-4d18-a4ad-2c025d473100EnglishSymplectic Elements at Oxford2010Brandl, KSun, LNeppl, CSiggs, OLe Gall, STomisato, WLi, XDu, XMaennel, DBlobel, CBeutler, BToll-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. |
| spellingShingle | Brandl, K Sun, L Neppl, C Siggs, O Le Gall, S Tomisato, W Li, X Du, X Maennel, D Blobel, C Beutler, B MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title | MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title_full | MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title_fullStr | MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title_full_unstemmed | MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title_short | MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. |
| title_sort | myd88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific egf receptor ligands |
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