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Review
. 2009 Jun;30(6):263-70.
doi: 10.1016/j.it.2009.04.001. Epub 2009 May 7.

A(2B) adenosine receptors in immunity and inflammation

György Haskó  1 , Balázs Csóka, Zoltán H Németh, E Sylvester Vizi, Pál Pacher
Affiliations
Review

A(2B) adenosine receptors in immunity and inflammation

György Haskó et al. Trends Immunol. 2009 Jun.

Abstract

A(2B) adenosine receptors are increasingly recognized as important orchestrators of inflammation. A(2B) receptor activation promotes the inflammatory response of mast cells, epithelial cells, smooth muscle cells and fibroblasts, thereby contributing to the pathophysiology of asthma and colitis. A(2B) receptor stimulation limits endothelial cell inflammatory responses and permeability and suppresses macrophage activation thereby preventing tissue injury after episodes of hypoxia and ischemia. A(2B) receptor stimulation also promotes the production of angiogenic cytokines by endothelial cells, mast cells and dendritic cells, aiding granuloma tissue formation and inflammatory resolution, but can also contribute to tumor growth. A(2B) receptors are, thus, potentially important pharmacological targets in treating immune system dysfunction and inflammation.

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Figures

Figure 1
Figure 1
A2B receptor activation on mast cells triggers the release of IL-4 and IL-8. Coupling of A2B receptors to Gq proteins activates PLCβ leading to elevations in intracellular Ca2+ levels and activation of the transcription factor NFAT, which in turn transactivates the IL-4 promoter and results in the release of IL-4. Coupling of A2B receptors to Gs proteins and subsequent accumulation of cAMP upregulates NFAT protein levels, amplifying the Gq-mediated IL-4 response. Gq and Gs protein-independent activation of p38 through the third intracellular loop of the A2B receptor leads to increased IL-8 transcription and release. Abbreviations: A2BAR, A2B adenosine receptor; cAMP, cyclic adenosine monophosphate; NFAT, nuclear factor of activated T cells; PLCβ, phospholipase C β.
Figure 2
Figure 2
Regulation of endothelial cell function by A2B receptors. During acute inflammation, A2B receptors suppress the expression of adhesion molecules on endothelial cells (EC), which leads to decreased leukocyte rolling, adhesion and transmigration. A2B receptors also prevent plasma leakage from the intravascular compartment into the tissue. During inflammatory resolution, A2B receptors facilitate endothelial cell proliferation and migration and promote the formation of blood vessels, effects that are mediated by the release of VEGF (vascular endothelial growth factor).
Figure 3
Figure 3
A2B receptors trigger the release of IL-6 by intestinal epithelial cells. Transmigrating neutrophils release ATP into the luminal compartment, where it is sequentially degraded to adenosine by CD39 and CD73 which are present on the brush border (apical side) of intestinal epithelial cells. Adenosine (ADO) released from transmigrated neutrophils activates luminal A2B receptors, which results in intracellular cAMP accumulation, and subsequently, increased transcription of IL-6 via activation of the transcription factors CREB and C/EBPβ.
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