Mice deficient in the CXCR2 ligand, CXCL1 (KC/GRO-α), exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis

Terez Shea-Donohue, Karen Thomas, M. Joshua Cody, Aiping Zhao, Louis J. Detolla, Karen M. Kopydlowski, Masayuki Fukata, Sergio A. Lira, Stefanie N. Vogel

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalInnate Immunity
Volume14
Issue number2
DOIs
StatePublished - Apr 2008

Keywords

  • CXCL1/KC
  • colitis
  • dextran sodium sulfate

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