A2B adenosine receptor gene deletion attenuates murine colitis

Gastroenterology. 2008 Sep;135(3):861-70. doi: 10.1053/j.gastro.2008.05.049. Epub 2008 May 21.


Background & aims: The A(2B) adenosine receptor (A(2B)AR) is the predominant adenosine receptor expressed in the colonic epithelia. We have previously shown that A(2B)AR mRNA and protein levels are up-regulated during colitis. In this study, we addressed the role of the A(2B)AR 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 A(2B)AR-null mice (A(2B)AR(-/-)). 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 A(2B)AR(-/-) compared with their wild-type counterparts. Clinical features, histologic score, and myeloperoxidase activity were significantly decreased in A(2B)AR(-/-) mice. However, A(2B)AR(-/-) showed increased susceptibility to systemic Salmonella infection. Tissue levels of the neutrophil chemokine, KC was decreased in colitic A(2B)AR(-/-) mice. In addition, flagellin-induced KC levels were attenuated in A(2B)AR(-/-) mice. Neutrophil chemotaxis in response to exogenous interleukin-8 was preserved in A(2B)AR(-/-) mice, suggesting intact neutrophil migration in response to appropriate stimuli.

Conclusions: These data demonstrate, for the first time, that the A(2B)AR plays a proinflammatory role in colitis. A(2B) receptor antagonism may be an effective treatment for acute inflammatory intestinal diseases such as acute flare of inflammatory bowel disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Migration Assays, Leukocyte
  • Chemokine CXCL1 / metabolism
  • Colitis / etiology
  • Colitis / genetics*
  • Colitis / pathology
  • Colitis / physiopathology*
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Disease Susceptibility
  • Female
  • Flagellin / pharmacology
  • Gene Deletion
  • Inflammation Mediators / metabolism
  • Interleukin-8 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / physiology
  • Peroxidase / metabolism
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / physiology*
  • Salmonella Infections / genetics
  • Salmonella Infections / pathology
  • Salmonella Infections / physiopathology
  • Salmonella typhimurium
  • Trinitrobenzenesulfonic Acid


  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Inflammation Mediators
  • Interleukin-8
  • Receptor, Adenosine A2B
  • Flagellin
  • Trinitrobenzenesulfonic Acid
  • Dextran Sulfate
  • Peroxidase