The A2B adenosine receptor protects against inflammation and excessive vascular adhesion

来自 EBSCO

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作者：

Y Dan，Z Ying，HG Nguyen，M Koupenova，AK Chauhan，M Makitalo，MR Jones，C St. Hilaire，DC Seldin，P Toselli

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摘要：

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.

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关键词：

Animals Mice, Knockout Mice Blood Vessels Bone Marrow Cells Inflammation Intercellular Adhesion Molecule-1 E-Selectin P-Selectin Receptor, Adenosine A2B