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

Abstract

BackgroundAdenosine, an endogenous purine nucleoside, is involved in several physiological functions. We have previously shown that A2BAR plays a pro-inflammatory role during colitis. AimsOur goals were to determine if A2BAR expression was necessary on immune cells/non-immune cells during colitis and if A2BAR was a suitable target for treating intestinal inflammation. MethodsWild-type and A2BAR knockout mice were utilized in bone marrow transplants to explore the importance of immune/non-immune A2BAR expression during the development of colitis. Additionally, a T-cell transfer model of colitis was used in Rag1 knockout or A2BAR/RAG1 double knockout recipients. Finally, A2BAR small interfering RNA nanoparticles were administered to dextran sodium sulphate-treated mice. ResultsWild-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 A2BAR/RAG1 double knockout recipients. Animals receiving nanoparticles exhibited attenuated parameters of colitis severity compared to mice receiving control nanoparticles. ConclusionsOur results suggest that A2BAR on non-immune cells plays an important role for the induction of colitis and targeting A2BAR expression during colitis may be useful for alleviating symptoms of intestinal inflammation.