A2BAR expression in non-immune cells plays an important role in the development of murine colitis.

Abstract: Background: Adenosine, an endogenous purine nucleoside, is involved in several physiological functions. We have previously shown that A_2BAR plays a pro-inflammatory role during colitis. Aims: Our goals were to determine if A_2BAR expression was necessary on immune cells/non-immune cells during colitis and if A_2BAR was a suitable target for treating intestinal inflammation. Methods: Wild-type and A_2BAR knockout mice were utilized in bone marrow transplants to explore the importance of immune/non-immune A_2BAR expression during the development of colitis. Additionally, a T-cell transfer model of colitis was used in Rag1 knockout or A_2BAR/RAG1 double knockout recipients. Finally, A_2BAR small interfering RNA nanoparticles were administered to dextran sodium sulphate-treated mice. Results: Wild-type mice receiving wild-type or knockout bone marrow developed severe colitis after dextran sodium sulphate treatment, whereas colitis was significantly attenuated in knockout mice receiving wild-type or knockout bone marrow. Colitis induced in Rag1 knockout animals was attenuated in A_2BAR/RAG1 double knockout recipients. Animals receiving nanoparticles exhibited attenuated parameters of colitis severity compared to mice receiving control nanoparticles. Conclusions: Our results suggest that A_2BAR on non-immune cells plays an important role for the induction of colitis and targeting A_2BAR expression during colitis may be useful for alleviating symptoms of intestinal inflammation. [Copyright &y& Elsevier]