| First Author | Yang D | Year | 2006 |
| Journal | J Clin Invest | Volume | 116 |
| Issue | 7 | Pages | 1913-23 |
| PubMed ID | 16823489 | Mgi Jnum | J:111715 |
| Mgi Id | MGI:3654766 | Doi | 10.1172/JCI27933 |
| Citation | Yang D, et al. (2006) The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116(7):1913-23 |
| abstractText | Adenosine has been described as playing a role in the control of inflammation, but it has not been certain which of its receptors mediate this effect. Here, we generated an A2B adenosine receptor-knockout/reporter gene-knock-in (A2BAR-knockout/reporter gene-knock-in) mouse model and showed receptor gene expression in the vasculature and macrophages, the ablation of which causes low-grade inflammation compared with age-, sex-, and strain-matched control mice. Augmentation of proinflammatory cytokines, such as TNF-alpha, and a consequent downregulation of IkappaB-alpha are the underlying mechanisms for an observed upregulation of adhesion molecules in the vasculature of these A2BAR-null mice. Intriguingly, leukocyte adhesion to the vasculature is significantly increased in the A2BAR-knockout mice. Exposure to an endotoxin results in augmented proinflammatory cytokine levels in A2BAR-null mice compared with control mice. Bone marrow transplantations indicated that bone marrow (and to a lesser extent vascular) A2BARs regulate these processes. Hence, we identify the A2BAR as a new critical regulator of inflammation and vascular adhesion primarily via signals from hematopoietic cells to the vasculature, focusing attention on the receptor as a therapeutic target. |
