Adenosine A3 receptors negatively regulate the engulfment-dependent apoptotic cell suppression of inflammation

Duró, Edina; Pallai, Anna; Köröskényi, Krisztina; Sarang, Zsolt; Szondy, Zsuzsanna

doi:10.1016/j.imlet.2014.06.014

Cited by 11 publications

(13 citation statements)

References 27 publications

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“…Indeed, the relatively poor anti-infective function of macrophages from human neonates is thought to reflect the dominance of A 3 expressed by these cells 80 . By contrast, studies have indicated that A 3 ligation diminishes the suppression of inflammation induced by engulfment of apoptotic cells 54 . In patients with RA, A 3 expression is a marker of disease severity and can predict the efficacy of treatment of symptoms with a selective adenosine receptor A 3 ligand (TABLE 1) 35 .…”

Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 95%

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Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis. Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of rheumatoid arthritis. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as Rheumatoid Arthritis, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs and the role of adenosine in fibrosis and fibrosing diseases will also be discussed.

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Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 95%

“…A 2a engagement promotes engulfment-mediated neutrophil downregulation, whereas A 3 engagement diminishes engulfment-mediated downregulation of proinflammatory actions (TABLE 1) 54,55 .…”

Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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“…1), apoptotic cells are engulfed by macrophages, and adenosine is produced in sufficient quantities to activate both A2ARs and A3Rs. A2AR signalling activates G s proteins and suppresses apoptotic cell-induced formation of the neutrophil migration factors CXCL1 (also known as KC) and CXCL2 (also known as MIP2) 90 (FIG. 4b).…”

Section: Monocytes Macrophages Dcs and Neutrophilsmentioning

confidence: 99%

“…As a result, the balance in the activation of A2ARs and A3Rs determines the amount of neutrophil chemoattractants formed. As the expression of A2ARs increases and A3Rs decreases over time during phagocytosis of apoptotic cells, adenosine gradually becomes more suppressive of the pro-inflammatory signals produced as a result of macrophage engulfment of apoptotic cells 90 .…”

Section: Monocytes Macrophages Dcs and Neutrophilsmentioning

confidence: 99%

Purinergic regulation of the immune system

2016

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Cellular stress or apoptosis triggers the release of ATP, ADP and other nucleotides into the extracellular space. Extracellular nucleotides function as autocrine and paracrine signalling molecules by activating cell-surface P2 purinergic receptors that elicit pro-inflammatory immune responses. Over time, extracellular nucleotides are metabolized to adenosine, leading to reduced P2 signalling and increased signalling through anti-inflammatory adenosine (P1 purinergic) receptors. Here, we review how local purinergic signalling changes over time during tissue responses to injury or disease, and we discuss the potential of targeting purinergic signalling pathways for the immunotherapeutic treatment of ischaemia, organ transplantation, autoimmunity or cancer.

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“…Adenosine then triggers macrophage adenosine A 2A receptors (A2ARs) to suppress the NO-dependent formation of neutrophil migration factors, such as macrophage inflammatory protein-2, via activating the adenylate cyclase/protein kinase A pathway ( 86 ). Interestingly, both adenosine A 2A and A 3 (A3R) receptors are expressed by macrophages, and while A2ARs inhibit, A3Rs promote the release of neutrophil migration factors by engulfing macrophages ( 87 ). However, while A2AR expression increases ( 86 ), A3R is downregulated during the course of efferocytosis ( 87 ) potentiating and maintaining this way the anti-inflammatory effects of adenosine.…”

Section: Apoptotic Cells Release Anti-inflammatory Moleculesmentioning

confidence: 99%

Anti-inflammatory Mechanisms Triggered by Apoptotic Cells during Their Clearance

et al. 2017

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In the human body, billions of cells die by apoptosis every day. The subsequent clearance of apoptotic cells by phagocytosis is normally efficient enough to prevent secondary necrosis and the consequent release of cell contents that would induce inflammation and trigger autoimmunity. In addition, apoptotic cells generally induce an anti-inflammatory response, thus removal of apoptotic cells is usually immunologically silent. Since the first discovery that uptake of apoptotic cells leads to transforming growth factor (TGF)-β and interleukin (IL)-10 release by engulfing macrophages, numerous anti-inflammatory mechanisms triggered by apoptotic cells have been discovered, including release of anti-inflammatory molecules from the apoptotic cells, triggering immediate anti-inflammatory signaling pathways by apoptotic cell surface molecules via phagocyte receptors, activating phagocyte nuclear receptors following uptake and inducing the production of anti-inflammatory soluble mediators by phagocytes that may act via paracrine or autocrine mechanisms to amplify and preserve the anti-inflammatory state. Here, we summarize our present knowledge about how these anti-inflammatory mechanisms operate during the clearance of apoptotic cells.

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Adenosine A3 receptors negatively regulate the engulfment-dependent apoptotic cell suppression of inflammation

Cited by 11 publications

References 27 publications

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Purinergic regulation of the immune system

Anti-inflammatory Mechanisms Triggered by Apoptotic Cells during Their Clearance

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