Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-α), exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis
| Autor: | Sergio A. Lira, Karen Thomas, M. Joshua Cody, Stefanie N. Vogel, Masayuki Fukata, Louis J. DeTolla, Karen M. Kopydlowski, Aiping Zhao, Terez Shea-Donohue |
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| Rok vydání: | 2008 |
| Předmět: |
Chemokine
Colon Neutrophils Chemokine CXCL1 animal diseases Immunology Inflammation Biology Microbiology Article Mice medicine Animals CXC chemokine receptors Colitis Molecular Biology Mice Knockout Innate immune system Dextran Sulfate Cell Biology medicine.disease Molecular biology Mice Inbred C57BL CXCL1 Infectious Diseases Neutrophil Infiltration biology.protein Disease Susceptibility medicine.symptom Infiltration (medical) Homeostasis |
| Zdroj: | Innate Immunity. 14:117-124 |
| ISSN: | 1753-4267 1753-4259 |
| DOI: | 10.1177/1753425908088724 |
| Popis: | The role of TLRs and MyD88 in the maintenance of gut integrity in response to dextran sodium sulfate (DSS)-induced colitis was demonstrated recently and led to the conclusion that the innate immune response to luminal commensal flora provides necessary signals that facilitate epithelial repair and permits a return to homeostasis after colonic injury. In this report, we demonstrate that a deficit in a single neutrophil chemokine, CXCL1/KC, also results in a greatly exaggerated response to DSS. Mice with a targeted mutation in the gene that encodes this chemokine responded to 2.5% DSS in their drinking water with significant weight loss, bloody stools, and a complete loss of gut integrity in the proximal and distal colon, accompanied by a predominantly mononuclear infiltrate, with few detectable neutrophils. In contrast, CXCL1/KC— /—and wild-type C57BL/6J mice provided water showed no signs of inflammation and, at this concentration of DSS, wild-type mice showed only minimal histopathology, but significantly more infiltrating neutrophils. This finding implies that neutrophil infiltration induced by CXCL1/KC is an essential component of the intestinal response to inflammatory stimuli as well as the ability of the intestine to restore mucosal barrier integrity. |
| Databáze: | OpenAIRE |
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