Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway

Tian, Ye; Piras, Bryan A.; Krön, Irving L.; French, Brent A.; Yang, Zequan

doi:10.1155/2015/585297

Cited by 49 publications

(46 citation statements)

References 40 publications

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“…As noted above, A 2b promotes a phenotypical switch from M1 to M2 macrophages, 75-77 but also stimulates the differentiation of dendritic cells, which can promote type 17 T helper cells (T H 17) immune responses via production of IL-6 87-89 . Indeed, in in vivo studies high concentrations of adenosine exacerbated arthritis and tissue destruction in rats via an A 2b mechanism 90 .…”

Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 91%

“…One mechanism by which A 2a ligation alters macrophage function is via stimulating expression of the orphan nuclear receptor NR4A, which diminishes activation of NFκB-dependent gene expression 73,74 . A 2b also stimulates the switch from an M1 to an M2 phenotype 75-77 . The role of A 3 in regulation of inflammatory macrophage function is less clear; A 3 stimulation clearly suppresses cytokine expression and release by macrophages and diminishes inflammation in mouse models of arthritis and inflammatory bowel disease 70,78-86 .…”

Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 99%

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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: 91%

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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“…M2-like macrophages activated by Tregs have well known anti-inflammatory characteristics and are an integral component of the wound-healing processes [45]. Consistently, experimental modulation of macrophage polarization towards an M2 state has been previously demonstrated to improve wound healing post-IR [46]. Alternative macrophage activation is initiated in response to IL-10 or TGF-β.…”

Section: Discussionmentioning

confidence: 96%

The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells

Xiao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice. Methods: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-β1 mAbs, 11) IL-2C+anti-IL-10 mAbs. The following parameters were measured at different time points: infarct area, myocardial apoptosis, splenocytes, the inhibitory function of Tregs, and presence of inflammatory factors. In addition, immunohistochemistry analysis was performed. Results: We observed that Tregs were activated in response to MIRI. IL-2C administered before MIRI induced Treg expansion in both spleen and heart, attenuated Th1 and Th17 cell numbers, improved myocardial function, and attenuated both infiltration of inflammatory cells and apoptosis after MIRI. Furthermore, IL-2C administration reduced expression of inflammatory cytokines in the heart and attenuated proliferation of splenic cells. Depletion of Tregs with anti-CD25 mAb abrogated the beneficial effects of IL-2C. However, IL-2C–mediated myocardial protection was not dependent on either IL-10 or TGF-β. In addition, IL-2C administration after MIRI did not reduce infarct area, but did improve myocardial function slightly and reduced myocardial fibrosis. Conclusion: Our results demonstrate that IL-2C–induced Treg expansion attenuates MIRI and improves myocardial recovery in vivo, suggesting that IL-2C is a promising therapeutic target for myocardial IRI.

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“…Negative Arrhythmia [190] Adaptation Hypertrophy Angiogenesis GS-6201 [191] Diabetes mellitus and hyperlipidemia NECA [192] ATL-801 [193] MRS-1754 [194] A 3 AR…”

Section: Inotropic and Adrenergic Controlmentioning

confidence: 99%

Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases

Effendi

Nagano

Kobayashi

et al. 2020

Cells

115

103

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Adenosine is involved in a range of physiological and pathological effects through membrane-bound receptors linked to G proteins. There are four subtypes of adenosine receptors, described as A1AR, A2AAR, A2BAR, and A3AR, which are the center of cAMP signal pathway-based drug development. Several types of agonists, partial agonists or antagonists, and allosteric substances have been synthesized from these receptors as new therapeutic drug candidates. Research efforts surrounding A1AR and A2AAR are perhaps the most enticing because of their concentration and affinity; however, as a consequence of distressing conditions, both A2BAR and A3AR levels might accumulate. This review focuses on the biological features of each adenosine receptor as the basis of ligand production and describes clinical studies of adenosine receptor-associated pharmaceuticals in human diseases.

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Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway

Cited by 49 publications

References 40 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

The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells

Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases

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