Research progress on metabolic pathway of adenosine and regulation of pro-inflammatory cytokines in cell injury_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SU Xiaoyang , LI Shaobin ,  YAN Yusheng

Department of Cardiothoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, P.R.China;

Corresponding author：

YAN Yusheng, Email: yanys@fimmu.com

Keywords：

Ischemia-reperfusion injury; adenosine triphophate; adenosine; inflammation

DOI：

10.7507/1007-4848.201803002

Video：

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Adenosine triphophate (ATP), substantially liberated from the injured cells, activates the inflammatory cells to secrete various inflammatory factors, thus triggering uncontrolled systemic inflammatory response and thrombosis with aggravating the degree of damage. Metabolic pathway of adenosine consists of adenosine (Ado) synthase CD39-CD73, nucleoside transporters (NTs) and termination system of adenosine deaminase (ADA) and adenosine kinase (ADK). As a " switch” of the inflammatory response, the metabolic pathway converts ATP (the pro-inflammatory cytokines) to Ado (the anti-inflammatory mediators), maintaining the homeostasis between pro-inflammatory and anti-inflammatory as well as affecting the outcome of the injury. This review focused on the recent progress of adenosine metabolic pathway in cell injury.

Citation： SU Xiaoyang, LI Shaobin, YAN Yusheng. Research progress on metabolic pathway of adenosine and regulation of pro-inflammatory cytokines in cell injury. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(12): 1091-1095. doi: 10.7507/1007-4848.201803002 Copy

1.	Savio LEB, de Andrade Mello P, da Silva CG, et al. The P2X7 receptor in inflammatory diseases: Angel or Demon? Front Pharmacol, 2018, 9: 52.
2.	Wu Q, Wang T, Chen S, et al. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J, 2018, 39(12): 1028-1037.
3.	Heusch G. Critical issues for the translation of cardioprotection. Circ Res, 2017, 120(9): 1477-1486.
4.	Idzko M, Ferrari D, Riegel AK, et al. Extracellular nucleotide and nucleoside signaling in vascular and blood disease. Blood, 2014, 124(7): 1029-1037.
5.	Faas MM, Sáez T, de Vos P. Extracellular ATP and adenosine: The Yin and Yang in immune responses? Mol Aspects Med, 2017, 55: 9-19.
6.	Kishore BK, Robson SC, Dwyer KM. CD39-adenosinergic axis in renal pathophysiology and therapeutics. Purinergic Signal, 2018, 14(2): 109-120.
7.	Bönner F, Borg N, Burghoff S, et al. Resident cardiac immune cells and expression of the ectonucleotidase enzymes CD39 and CD73 after ischemic injury. PLoS One, 2012, 7(4): e34730.
8.	Takahashi-Sato K, Murakawa M, Kimura J, et al. Loss of ectonucleotidases from the coronary vascular bed after ischemia-reperfusion in isolated rat heart. BMC Cardiovasc Disord, 2013, 13: 53.
9.	Smith SB, Xu Z, Novitskaya T, et al. Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice. Life Sci, 2017, 179: 54-59.
10.	Aldi S, Marino A, Tomita K, et al. E-NTPDase1/CD39 modulates renin release from heart mast cells during ischemia/reperfusion: a novel cardioprotective role. FASEB J, 2015, 29(1): 61-69.
11.	Cai M, Huttinger ZM, He H, et al. Transgenic over expression of ectonucleotide triphosphate diphosphohydrolase-1 protects against murine myocardial ischemic injury. J Mol Cell Cardiol, 2011, 51(6): 927-935.
12.	Baek AE, Sutton NR, Petrovic-Djergovic D, et al. Ischemic cerebroprotection conferred by myeloid lineage-restricted or global CD39 transgene expression. Circulation, 2017, 135(24): 2389-2402.
13.	Roberts V, Campbell DJ, Lu B, et al. The differential effect of apyrase treatment and hCD39 overexpression on chronic renal fibrosis after ischemia-reperfusion injury. Transplantation, 2017, 101(7): e194-e204.
14.	Roberts V, Stagg J, Dwyer KM. The role of ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation. Front Immunol, 2014, 5: 64.
15.	Yoshida O, Kimura S, Jackson EK, et al. CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia-reperfusion injury in mice. Hepatology, 2013, 58(6): 2163-2175.
16.	Pommey S, Lu B, McRae J, et al. Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells. Hepatology, 2013, 57(4): 1597-1606.
17.	Ziegler M, Hohmann JD, Searle AK, et al. A single-chain antibody-CD39 fusion protein targeting activated platelets protects from cardiac ischaemia/reperfusion injury. Eur Heart J, 2018, 39(2): 111-116.
18.	Sashindranath M, Dwyer KM, Dezfouli S, et al. Development of a novel strategy to target CD39 antithrombotic activity to the endothelial-platelet microenvironment in kidney ischemia-reperfusion injury. Purinergic Signal, 2017, 13(2): 259-265.
19.	Wolff G, Truse R, Decking U. Extracellular adenosine formation by ecto-5′-nucleotidase (CD73) is no essential trigger for early phase ischemic preconditioning. PLoS One, 2015, 10(8): e0135086.
20.	Böring YC, Flögel U, Jacoby C, et al. Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis. Cardiovasc Res, 2013, 97(1): 88-96.
21.	Borg N, Alter C, Görldt N, et al. CD73 on T cells orchestrates cardiac wound healing after myocardial infarction by purinergic metabolic reprogramming. Circulation, 2017, 136(3): 297-313.
22.	Shin EY, Wang L, Zemskova M, et al. Adenosine production by biomaterial-supported mesenchymal stromal cells reduces the innate inflammatory response in myocardial ischemia/reperfusion injury. J Am Heart Assoc, 2018, 7(2): pii: e006949.
23.	Persson JN, Baird CH, Tong S, et al. Infant cardiopulmonary bypass: CD73 kinetics, association with clinical outcomes, and influence on serum adenosine production capacity. Pediatr Res, 2018, 83(4): 858-865.
24.	Yang C, Leung GP. Equilibrative nucleoside transporters 1 and 4: Which one is a better target for cardioprotection against ischemia-reperfusion injury? J Cardiovasc Pharmacol, 2015, 65(6): 517-521.
25.	Birnbaum Y, Birnbaum GD, Birnbaum I, et al. Ticagrelor and rosuvastatin have additive cardioprotective effects via adenosine. Cardiovasc Drugs Ther, 2016, 30(6): 539-550.
26.	Zimmerman MA, Tak E, Ehrentraut SF, et al. Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion. Hepatology, 2013, 58(5): 1766-1778.
27.	Rose JB, Naydenova Z, Bang A, et al. Equilibrative nucleoside transporter 1 plays an essential role in cardioprotection. Am J Physiol Heart Circ Physiol, 2010, 298(3): H771-H777.
28.	Pimentel VC, Moretto MB, Oliveira MC, et al. Neuroinflammation after neonatal hypoxia-ischemia is associated with alterations in the purinergic system: adenosine deaminase 1 isoenzyme is the most predominant after insult. Mol Cell Biochem, 2015, 403(1-2): 169-177.
29.	Tamura R, Ohta H, Satoh Y, et al. Neuroprotective effects of adenosine deaminase in the striatum. J Cereb Blood Flow Metab, 2016, 36(4): 709-720.
30.	Gracia E, Farré D, Cortés A, et al. The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. FASEB J, 2013, 27(3): 1048-1061.
31.	Cortés A, Gracia E, Moreno E, et al. Moonlighting adenosine deaminase: a target protein for drug development. Med Res Rev, 2015, 35(1): 85-125.
32.	Pignataro G, Maysami S, Studer FE, et al. Downregulation of hippocampal adenosine kinase after focal ischemia as potential endogenous neuroprotective mechanism. J Cereb Blood Flow Metab, 2008, 28(1): 17-23.
33.	Xu Y, Wang Y, Yan S, et al. Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation. Nat Commun, 2017, 8(1): 943.
34.	Vecchio EA, White PJ, May LT. Targeting adenosine receptors for the treatment of cardiac fibrosis. Front Pharmacol, 2017, 8: 243.
35.	Borea PA, Gessi S, Merighi S, et al. Pathological overproduction: the bad side of adenosine. Br J Pharmacol, 2017, 174(13): 1945-1960.
36.	Dai Y, Zhang W, Wen J, et al. A2B adenosine receptor-mediated induction of IL-6 promotes CKD. J Am Soc Nephrol, 2011, 22(5): 890-901.

1. Savio LEB, de Andrade Mello P, da Silva CG, et al. The P2X7 receptor in inflammatory diseases: Angel or Demon? Front Pharmacol, 2018, 9: 52.
2. Wu Q, Wang T, Chen S, et al. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J, 2018, 39(12): 1028-1037.
3. Heusch G. Critical issues for the translation of cardioprotection. Circ Res, 2017, 120(9): 1477-1486.
4. Idzko M, Ferrari D, Riegel AK, et al. Extracellular nucleotide and nucleoside signaling in vascular and blood disease. Blood, 2014, 124(7): 1029-1037.
5. Faas MM, Sáez T, de Vos P. Extracellular ATP and adenosine: The Yin and Yang in immune responses? Mol Aspects Med, 2017, 55: 9-19.
6. Kishore BK, Robson SC, Dwyer KM. CD39-adenosinergic axis in renal pathophysiology and therapeutics. Purinergic Signal, 2018, 14(2): 109-120.
7. Bönner F, Borg N, Burghoff S, et al. Resident cardiac immune cells and expression of the ectonucleotidase enzymes CD39 and CD73 after ischemic injury. PLoS One, 2012, 7(4): e34730.
8. Takahashi-Sato K, Murakawa M, Kimura J, et al. Loss of ectonucleotidases from the coronary vascular bed after ischemia-reperfusion in isolated rat heart. BMC Cardiovasc Disord, 2013, 13: 53.
9. Smith SB, Xu Z, Novitskaya T, et al. Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice. Life Sci, 2017, 179: 54-59.
10. Aldi S, Marino A, Tomita K, et al. E-NTPDase1/CD39 modulates renin release from heart mast cells during ischemia/reperfusion: a novel cardioprotective role. FASEB J, 2015, 29(1): 61-69.
11. Cai M, Huttinger ZM, He H, et al. Transgenic over expression of ectonucleotide triphosphate diphosphohydrolase-1 protects against murine myocardial ischemic injury. J Mol Cell Cardiol, 2011, 51(6): 927-935.
12. Baek AE, Sutton NR, Petrovic-Djergovic D, et al. Ischemic cerebroprotection conferred by myeloid lineage-restricted or global CD39 transgene expression. Circulation, 2017, 135(24): 2389-2402.
13. Roberts V, Campbell DJ, Lu B, et al. The differential effect of apyrase treatment and hCD39 overexpression on chronic renal fibrosis after ischemia-reperfusion injury. Transplantation, 2017, 101(7): e194-e204.
14. Roberts V, Stagg J, Dwyer KM. The role of ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation. Front Immunol, 2014, 5: 64.
15. Yoshida O, Kimura S, Jackson EK, et al. CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia-reperfusion injury in mice. Hepatology, 2013, 58(6): 2163-2175.
16. Pommey S, Lu B, McRae J, et al. Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells. Hepatology, 2013, 57(4): 1597-1606.
17. Ziegler M, Hohmann JD, Searle AK, et al. A single-chain antibody-CD39 fusion protein targeting activated platelets protects from cardiac ischaemia/reperfusion injury. Eur Heart J, 2018, 39(2): 111-116.
18. Sashindranath M, Dwyer KM, Dezfouli S, et al. Development of a novel strategy to target CD39 antithrombotic activity to the endothelial-platelet microenvironment in kidney ischemia-reperfusion injury. Purinergic Signal, 2017, 13(2): 259-265.
19. Wolff G, Truse R, Decking U. Extracellular adenosine formation by ecto-5′-nucleotidase (CD73) is no essential trigger for early phase ischemic preconditioning. PLoS One, 2015, 10(8): e0135086.
20. Böring YC, Flögel U, Jacoby C, et al. Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis. Cardiovasc Res, 2013, 97(1): 88-96.
21. Borg N, Alter C, Görldt N, et al. CD73 on T cells orchestrates cardiac wound healing after myocardial infarction by purinergic metabolic reprogramming. Circulation, 2017, 136(3): 297-313.
22. Shin EY, Wang L, Zemskova M, et al. Adenosine production by biomaterial-supported mesenchymal stromal cells reduces the innate inflammatory response in myocardial ischemia/reperfusion injury. J Am Heart Assoc, 2018, 7(2): pii: e006949.
23. Persson JN, Baird CH, Tong S, et al. Infant cardiopulmonary bypass: CD73 kinetics, association with clinical outcomes, and influence on serum adenosine production capacity. Pediatr Res, 2018, 83(4): 858-865.
24. Yang C, Leung GP. Equilibrative nucleoside transporters 1 and 4: Which one is a better target for cardioprotection against ischemia-reperfusion injury? J Cardiovasc Pharmacol, 2015, 65(6): 517-521.
25. Birnbaum Y, Birnbaum GD, Birnbaum I, et al. Ticagrelor and rosuvastatin have additive cardioprotective effects via adenosine. Cardiovasc Drugs Ther, 2016, 30(6): 539-550.
26. Zimmerman MA, Tak E, Ehrentraut SF, et al. Equilibrative nucleoside transporter (ENT)-1-dependent elevation of extracellular adenosine protects the liver during ischemia and reperfusion. Hepatology, 2013, 58(5): 1766-1778.
27. Rose JB, Naydenova Z, Bang A, et al. Equilibrative nucleoside transporter 1 plays an essential role in cardioprotection. Am J Physiol Heart Circ Physiol, 2010, 298(3): H771-H777.
28. Pimentel VC, Moretto MB, Oliveira MC, et al. Neuroinflammation after neonatal hypoxia-ischemia is associated with alterations in the purinergic system: adenosine deaminase 1 isoenzyme is the most predominant after insult. Mol Cell Biochem, 2015, 403(1-2): 169-177.
29. Tamura R, Ohta H, Satoh Y, et al. Neuroprotective effects of adenosine deaminase in the striatum. J Cereb Blood Flow Metab, 2016, 36(4): 709-720.
30. Gracia E, Farré D, Cortés A, et al. The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. FASEB J, 2013, 27(3): 1048-1061.
31. Cortés A, Gracia E, Moreno E, et al. Moonlighting adenosine deaminase: a target protein for drug development. Med Res Rev, 2015, 35(1): 85-125.
32. Pignataro G, Maysami S, Studer FE, et al. Downregulation of hippocampal adenosine kinase after focal ischemia as potential endogenous neuroprotective mechanism. J Cereb Blood Flow Metab, 2008, 28(1): 17-23.
33. Xu Y, Wang Y, Yan S, et al. Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation. Nat Commun, 2017, 8(1): 943.
34. Vecchio EA, White PJ, May LT. Targeting adenosine receptors for the treatment of cardiac fibrosis. Front Pharmacol, 2017, 8: 243.
35. Borea PA, Gessi S, Merighi S, et al. Pathological overproduction: the bad side of adenosine. Br J Pharmacol, 2017, 174(13): 1945-1960.
36. Dai Y, Zhang W, Wen J, et al. A2B adenosine receptor-mediated induction of IL-6 promotes CKD. J Am Soc Nephrol, 2011, 22(5): 890-901.

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