A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis

Vasantha L. Kolachala, Matam Vijay-Kumar, Guillaiume Dalmasso, Dan Yang, Joel Linden, Lixin Wang, Andrew Gewirtz, Katya Ravid, Didier Merlin, Shanthi V. Sitaraman

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Background & Aims: The A2B adenosine receptor (A2BAR) is the predominant adenosine receptor expressed in the colonic epithelia. We have previously shown that A2BAR mRNA and protein levels are up-regulated during colitis. In this study, we addressed the role of the A2BAR in the development of murine colitis and the potential mechanism underlying its effects. Methods: Dextran sodium sulfate (DSS), 2,4,6-trinitrobenzene sulfonic acid (TNBS), and Salmonella typhimurium were used to induce colitis in A2BAR-null mice (A2BAR-/-). Colitis was determined using established clinical and histologic scoring. Keratinocyte-derived chemokine (KC) measurements were performed using an enzyme-linked immunosorbent assay. Results: Colonic inflammation induced by DSS, TNBS, or S typhimurium was attenuated in A2BAR-/- compared with their wild-type counterparts. Clinical features, histologic score, and myeloperoxidase activity were significantly decreased in A2BAR-/- mice. However, A2BAR-/- showed increased susceptibility to systemic Salmonella infection. Tissue levels of the neutrophil chemokine, KC was decreased in colitic A2BAR-/- mice. In addition, flagellin-induced KC levels were attenuated in A2BAR-/- mice. Neutrophil chemotaxis in response to exogenous interleukin-8 was preserved in A2BAR-/- mice, suggesting intact neutrophil migration in response to appropriate stimuli. Conclusions: These data demonstrate, for the first time, that the A2BAR plays a proinflammatory role in colitis. A2B receptor antagonism may be an effective treatment for acute inflammatory intestinal diseases such as acute flare of inflammatory bowel disease.

Original languageEnglish (US)
Pages (from-to)861-870
Number of pages10
JournalGastroenterology
Volume135
Issue number3
DOIs
StatePublished - Sep 2008

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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