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 journalArticle

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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 - Jan 1 2008

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Adenosine A2B Receptors
Gene Deletion
Colitis
Dextran Sulfate
Neutrophils
Sulfonic Acids
Trinitrobenzenes
Flagellin
Intestinal Diseases
Purinergic P1 Receptors
Salmonella Infections
Chemotaxis
Salmonella typhimurium
Interleukin-8
Inflammatory Bowel Diseases
Chemokines
Peroxidase

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Kolachala, V. L., Kumar, M. V., Dalmasso, G., Yang, D., Linden, J., Wang, L., ... Sitaraman, S. V. (2008). A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis. Gastroenterology, 135(3), 861-870. https://doi.org/10.1053/j.gastro.2008.05.049
Kolachala, Vasantha L. ; Kumar, Matam Vijay ; Dalmasso, Guillaiume ; Yang, Dan ; Linden, Joel ; Wang, Lixin ; Gewirtz, Andrew ; Ravid, Katya ; Merlin, Didier ; Sitaraman, Shanthi V. / A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis. In: Gastroenterology. 2008 ; Vol. 135, No. 3. pp. 861-870.
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Kolachala, VL, Kumar, MV, Dalmasso, G, Yang, D, Linden, J, Wang, L, Gewirtz, A, Ravid, K, Merlin, D & Sitaraman, SV 2008, 'A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis', Gastroenterology, vol. 135, no. 3, pp. 861-870. https://doi.org/10.1053/j.gastro.2008.05.049

A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis. / Kolachala, Vasantha L.; Kumar, Matam Vijay; Dalmasso, Guillaiume; Yang, Dan; Linden, Joel; Wang, Lixin; Gewirtz, Andrew; Ravid, Katya; Merlin, Didier; Sitaraman, Shanthi V.

In: Gastroenterology, Vol. 135, No. 3, 01.01.2008, p. 861-870.

Research output: Contribution to journalArticle

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T1 - A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis

AU - Kolachala, Vasantha L.

AU - Kumar, Matam Vijay

AU - Dalmasso, Guillaiume

AU - Yang, Dan

AU - Linden, Joel

AU - Wang, Lixin

AU - Gewirtz, Andrew

AU - Ravid, Katya

AU - Merlin, Didier

AU - Sitaraman, Shanthi V.

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Y1 - 2008/1/1

N2 - 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.

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Kolachala VL, Kumar MV, Dalmasso G, Yang D, Linden J, Wang L et al. A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis. Gastroenterology. 2008 Jan 1;135(3):861-870. https://doi.org/10.1053/j.gastro.2008.05.049