Adenosine A2A receptor activation limits chronic granulomatous disease-induced hyperinflammation

Chehata, Veronica; Domeier, Phillip P; Weilnau, Justin N.; Lappas, Courtney M.

doi:10.1016/j.cellimm.2010.11.002

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…[7][8][9][10] The zeatin riboside (and CGS21680)-mediated inhibition of proinflamamtory cytokine production by both CD4 1 and CD8 1 T lymphocytes was potently blocked by cotreatment with 10 mM of the selective A 2A R antagonist, ZM241385. Similar doses of ZM241385 have previously been established to inhibit A 2A R-mediated effects in T lymphocytes.…”

Section: Cd8mentioning

confidence: 99%

The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation

Lappas

2014

Cell Mol Immunol

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Cytokinins are plant hormones that play an integral role in multiple aspects of plant growth and development. The biological functions of cytokinins in mammalian systems are, however, largely uncharacterized. The naturally occurring cytokinin zeatin riboside has recently been demonstrated to activate the mammalian adenosine A 2A receptor, which is broadly expressed by various cell types including immune system cells, with the activation of the A 2A R playing a role in the regulation of cells involved in both innate and adaptive immunity. We show for the first time that zeatin riboside modulates mammalian immune system activity via an A 2A R-dependent mechanism. Specifically, zeatin riboside treatment induces the production of cyclic adenosine monophosphate (cAMP) by T lymphocytes and inhibits the production by CD31 CD4 1 T cells of interferon (IFN)-c, IL-2, tumor-necrosis factor (TNF)-a, IL-4 and IL-13, and the production by CD31 CD8 1 T cells of IFN-c, IL-2 and TNF-a. Additionally, the upregulation of CD25, CD69 and CD40L by activated T lymphocytes is modulated by zeatin riboside. Zeatin riboside treatment also potently inhibits thioglycollate-induced peritoneal leukocytosis. The immunomodulatory activities of zeatin riboside are blocked by co-treatment with the selective A 2A R antagonist ZM241385. These data suggest that zeatin riboside possesses therapeutic potential as a mammalian immunomodulatory agent.

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Section: Cd8mentioning

confidence: 99%

The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation

Lappas

2014

Cell Mol Immunol

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“…CGS21680 (Sigma‐Aldrich) is a commercially available A 2A R agonist that has been shown to be efficacious in injury models (23, 24). The K i values of CGS21680 at A 1 , A 2A , A2 B , and A 3 receptors are >350 nM, 15 nM, >100 μM, and >1 mM, respectively (25).…”

Section: Methodsmentioning

confidence: 99%

Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms

et al. 2013

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Activation of the adenosine 2A receptor (A2AR) reduces inflammation in models of acute injury but contribution in development of chronic abdominal aortic aneurysms (AAAs) is unknown. Elastase perfusion to induce AAA formation in A2AR-knockout (A2ARKO) and C57BL6/J wild-type (WT) mice resulted in nearly 100% larger aneurysms in A2ARKO compared to WT at d 14 (P<0.05), with evidence of greater elastin fragmentation, more immune cell infiltration, and increased matrix metallatoproteinase (MMP) 9 expression (P<0.05). Separately, exogenous A2AR antagonism in elastase-perfused WT mice also resulted in larger aneurysms (P<0.05), while A2AR agonism limited aortic dilatation (P<0.05). Activated Thy-1.2(+) T lymphocytes from WT mice treated in vitro with A2AR antagonist increased cytokine production, and treatment with A2AR agonist decreased cytokine production (P<0.05 for all). Primary activated CD4(+) T lymphocytes from A2ARKO mice exhibited greater chemotaxis (P<0.05). A2AR antagonist increased chemotaxis of activated CD4(+) cells from WT mice in vitro, and A2AR agonist reduced this effect (P<0.05). A2AR activation attenuates AAA formation partly by inhibiting immune cell recruitment and reducing elastin fragmentation. These findings support augmenting A2AR signaling as a putative target for limiting aneurysm formation.

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Immunological alterations mediated by adenosine during host-microbial interactions

et al. 2011

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Adenosine accumulates in inflammation and ischemia but it is more than an end-product of ATP catabolism. Signaling through different receptors with distinct, cell-specific cytoplasmic pathways, adenosine is now recognized as an inducible switch that regulates the immune system. By acting through the A2AAR, adenosine shapes T cell function, largely by conferring an anti-inflammatory tone on effector Th cells (Teff) and natural killer (NK)T cells. In contrast, both the A2AAR and A2BAR are expressed by antigen-presenting cells (APC) which have been shown to regulate innate responses and the transition to adaptive immunity. There is also emerging evidence that adenosine production is one mechanism that allows some pathogens as well as neoplasms to evade host defenses. This review discusses the immunoregulatory functions of adenosine and some of the interactions it may have in regulating host–microbial interactions.

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Adenosine A2A receptor activation limits chronic granulomatous disease-induced hyperinflammation

Cited by 3 publications

References 56 publications

The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation

The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation

Adenosine 2A receptor modulates inflammation and phenotype in experimental abdominal aortic aneurysms

Immunological alterations mediated by adenosine during host-microbial interactions

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