Journal article
The A2B adenosine receptor protects against inflammation and excessive vascular adhesion
The Journal of clinical investigation, Vol.116(7), pp.1913-1923
07/2006
DOI: 10.1172/JCI27933
PMCID: PMC1483170
PMID: 16823489
Abstract
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.
Details
- Title: Subtitle
- The A2B adenosine receptor protects against inflammation and excessive vascular adhesion
- Creators
- Dan Yang - Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USAYing ZhangHao G NguyenMilka KoupenovaAnil K ChauhanMaria MakitaloMatthew R JonesCynthia St HilaireDavid C SeldinPaul ToselliEdward LampertiBarbara M SchreiberHaralambos GavrasDenisa D WagnerKatya Ravid
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.116(7), pp.1913-1923
- DOI
- 10.1172/JCI27933
- PMID
- 16823489
- PMCID
- PMC1483170
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- P01 HL013262 / NHLBI NIH HHS HL13262 / NHLBI NIH HHS R37 HL041002 / NHLBI NIH HHS 41002 / PHS HHS
- Language
- English
- Date published
- 07/2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094312802771
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