Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction

Takahashi, Hideo; Ishibashi, Hiromi; Hamano, Ryosuke; Kanke, Toru; Liu, Keyue; Shinmoto, Hiroshi; Yagi, T.; Yoshino, Tadashi; Sendo, Toshiaki; Tanaka, Noriaki; Nishibori, Masahiro

doi:10.1016/j.ejphar.2007.02.005

Cited by 22 publications

(21 citation statements)

References 28 publications

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“…Cd73-/- mice have 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through high endothelial venules compared with wild-type mice after LPS administration 67 . The endothelial A 2B R is a likely target of CD73-generated adenosine and inhibits the adhesion of lymphocytes 67 and other leukocytes 68, 69 .…”

Section: Interface Between Lymphocytes and The Vasculaturementioning

confidence: 99%

Regulation of Lymphocyte Function by Adenosine

Linden¹,

Cekic²

2012

ATVB

129

103

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Adenosine regulates the interaction between lymphocytes and the vasculature and is important for controlling lymphocyte trafficking in response to tissue injury or infection. Adenosine can blunt the effects of T cell receptor (TCR) activation primarily by activating adenosine A2A receptors (A2AR) and signaling via cyclic AMP and protein kinase A (PKA). PKA reduces proximal TCR signaling by phosphorylation of C-terminal Src kinase (Csk), nuclear factor of activated T cells (NF-AT) and cyclic AMP response element binding protein (CREB). PKA activation can either enhance or inhibit the survival of T cells depending on the strength and duration of signaling. Inducible enzymes such as CD73 and CD39 regulate adenosine formation and degradation in vivo. The extravasation of lymphocytes through blood vessels is influenced by A2AR-mediated suppression of Intercellular Adhesion Molecule 1 (ICAM) expression on lymphocytes and diminished production of IFNγ and IFNγ-inducible chemokines that are chemotactic to activated lymphocytes. Adenosine also decreases the barrier function of vascular endothelium by activating A2BRs. In sum, adenosine signaling is influenced by tissue inflammation and injury through induction of receptors and enzymes and has generally inhibitory effects on lymphocyte migration into inflamed tissues due to PKA-mediated effects on adhesion molecules, IFNγ production and endothelial barrier function.

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Section: Interface Between Lymphocytes and The Vasculaturementioning

confidence: 99%

Regulation of Lymphocyte Function by Adenosine

Linden¹,

Cekic²

2012

ATVB

129

103

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“…Gessi et al24 obtained also evidence for a rapid upregulation of A 3 receptors upon activation of human T lymphocytes. In addition, recent findings indicate that the activation of A 3 receptors in human lymphocytes blunts the inhibitory effects exerted by adenosine or the A 2a receptor agonist CGS 21680 on cell proliferation, suggesting that different receptors mediate opposite regulatory actions of adenosine in these cells 25. Nevertheless, the paucity of data regarding the expression and function of A 3 receptors in lymphocytes deserves further investigation, particularly to clarify the suitability of experimental models and their differences among species, as well as to verify whether experimental findings can be translated to humans or the gut immune system.…”

Section: Regulatory Actions Of Adenosine On Immune‐inflammatory Cellsmentioning

confidence: 99%

Pharmacological modulation of adenosine system: Novel options for treatment of inflammatory bowel diseases

Antonioli

Fornai

Colucci

et al. 2008

Inflammatory Bowel Diseases

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Inflammatory bowel diseases (IBDs) are chronic disorders resulting from abnormal and persistent immune responses which lead to severe tissue injury and disturbances in digestive motor/secretory functions. At present, pharmacotherapy represents the cornerstone for the management of IBDs, and recent advances in understanding the immunopathogenesis of intestinal inflammation suggest the adenosine system as an attractive target for development of novel drugs against gut inflammatory disorders. Consistent evidence indicates that adenosine plays a relevant role in the regulation of immune system via interaction with specific cell-membrane G-protein-coupled receptors (A(1), A(2a), A(2b), and A(3)). Moreover, this nucleoside is implicated in the control of enteric neurotransmission and gut motor functions. In the presence of inflammation, the adenosine system acts as a sensible sensor apparatus, which, through dynamic modifications in the expression of ecto-enzymes and purinergic receptors, adapts its metabolism to tissue health status and contributes to the mechanisms deputed to the protection of tissues against inflammatory injuries. In keeping with these concepts, it is becoming increasingly appreciated that drugs targeted on adenosine receptors or enzymes responsible for adenosine catabolism can exert beneficial effects on experimental models of intestinal inflammation. This review aims to discuss the role of adenosine in the regulation of enteric immune responses and gut neuromuscular functions in the presence of inflammation, as well as to highlight the mechanisms through which the pharmacological modulation of adenosine pathways may have potential applications for the therapeutic management of IBDs.

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“…A 2A AR s are widely expressed in cells such as monocytes, lymphocytes, and mast cells, which are involved in the innate immunity [189,190]. Increase evidence show that A 2A AR s have a role in the physiologic immunosuppressive pathway that protects normal tissues from collateral damage by overactive immune cells and their proinflammatory cytokines [191].…”

Section: Inflammatory Diseasesmentioning

confidence: 98%

Adenosine Receptors: What We Know and What We are Learning

Trincavelli¹,

Daniele²,

Martini

2010

CTMC

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Adenosine, beside its role in the intermediate metabolism, mediates its physiological functions by interacting with four receptor subtypes named A(1), A(2A), A(2B) and A(3). All these receptors belong to the superfamily of G protein-coupled receptors that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body, they are involved in a variety of physiological processes and pathology including neurological, cardiovascular, inflammatory diseases and cancer. At now, it is ascertained that the biological responses evoked by the activation of a single receptor are the result of complex and integrated signalling pathways targeted by different receptor proteins, interacting each other. These pathways may in turn control receptor responsiveness over time through fine regulatory mechanisms including desensitization-internalization processes. The knowledge of adenosine receptor structure as well as the molecular mechanisms underlying the regulation of receptor functioning and of receptor-receptor interactions during physio and pathological conditions represent a pivotal starting point to the development of new drugs with high efficacy and selectivity for each adenosine receptor subtype. The goal of this review is to summarize what we now and what we are learning about adenosine receptor structure, signalling and regulatory mechanisms. In addition, to dissect the potential therapeutic application of adenosine receptor ligands, the pathophysiological role of the receptor subtypes in different tissues are discussed.

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Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction

Cited by 22 publications

References 28 publications

Regulation of Lymphocyte Function by Adenosine

Regulation of Lymphocyte Function by Adenosine

Pharmacological modulation of adenosine system: Novel options for treatment of inflammatory bowel diseases

Adenosine Receptors: What We Know and What We are Learning

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