A(2B)AR expression in non-immune cells plays an important role in the development of murine colitis

作者：Ingersoll, Sarah A^*; Laroui, Hamed; Kolachala, Vasantha L; Wang, Lixin; Garg, Pallavi; Denning, Timothy L; Gewirtz, Andrew T; Merlin, Didier; Sitaraman, Shanthi V

来源：Digestive and Liver Disease, 2012, 44(10): 819-826.

DOI：10.1016/j.dld.2012.05.013

• A(2B) receptor
• Inflammation
• Nanoparticle therapy

Background: Adenosine, an endogenous purine nucleoside, is involved in several physiological functions. We have previously shown that A(2B)AR plays a pro-inflammatory role during colitis.
Aims: Our goals were to determine if A(2B)AR expression was necessary on immune cells/non-immune cells during colitis and if A(2B)AR was a suitable target for treating intestinal inflammation.
Methods: Wild-type and A(2B)AR knockout mice were utilized in bone marrow transplants to explore the importance of immune/non-immune A(2B)AR expression during the development of colitis. Additionally, a T-cell transfer model of colitis was used in Rag1 knockout or A(2B)AR/RAG1 double knockout recipients. Finally, A(2B)AR 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(2B)AR/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(2B)AR on non-immune cells plays an important role for the induction of colitis and targeting A(2B)AR expression during colitis may be useful for alleviating symptoms of intestinal inflammation.

• 出版日期2012-10