Format

Send to

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

A2B adenosine receptor gene deletion attenuates murine colitis.

Author information

1
Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

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.

PMID:
18601927
PMCID:
PMC2632861
DOI:
10.1053/j.gastro.2008.05.049
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center