The Adenosine System at the Crossroads of Intestinal Inflammation and Neoplasia

International Journal of Molecular Sciences

卷:21

Vanessa D’Antongiovanni¹  Matteo Fornai¹  Corrado Blandizzi¹  Laura Benvenuti¹  Luca Antonioli¹  Carolina Pellegrini² 

[1] Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy;

[2] Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy;

关键词: adenosine;    adenosine receptors;    inflammatory bowel diseases;    colitis-associated cancer;    colorectal cancer;    dextran sulfate sodium (DSS)-induced colitis;   

DOI  :  10.3390/ijms21145089

来源: DOAJ

【 摘 要 】

Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A₁ receptor subtype (A₁), A_2A, A_2B, and A₃. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage. However, a prolonged persistence of increased adenosine concentrations can be deleterious, participating in the creation of an immunosuppressed niche, ideal for neoplasia onset and development. Based on this evidence, the present review has been conceived to provide a comprehensive and critical overview of the involvement of adenosine system in shaping the molecular mechanisms underlying the enteric chronic inflammation and in promoting the generation of an immunosuppressive niche useful for the colorectal tumorigenesis.

【 授权许可】

Unknown