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


OBJECTIVE
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.
Center for Diagnostics & Therapeutics, Department of Biology, Georgia State University, Atlanta, GA, United States. singersoll@gsu.edu
Sarah A
SA
Ingersoll
Hamed
H
Laroui
Vasantha L
VL
Kolachala
Lixin
L
Wang
Pallavi
P
Garg
Timothy L
TL
Denning
Andrew T
AT
Gewirtz
Didier
D
Merlin
Shanthi V
SV
Sitaraman
D000818:Animals; D016026:Bone Marrow Transplantation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles; D012333:RNA, Messenger / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; D016264:Dextran Sulfate