A_2BAR expression in non-immune cells plays an important role in the development of murine colitis

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• 作者：Sarah A. Ingersoll ; Hamed Laroui ; Vasantha L. Kolachala ; Lixin Wang ; Pallavi Garg ; Timothy L. Denning ; Andrew T. Gewirtz ; Didier Merlin ; Shanthi V. Sitaraman
• 关键词：A2B receptor ; Inflammation ; Nanoparticle therapy
• 刊名：Digestive and Liver Disease
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：44
• 期：10
• 页码：819-826
• 全文大小：1601 K

文摘

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.