The hypoxia-inflammation link and potential drug targets

Current Opinion in Anaesthesiology

Volumn 24, Issue 4, 2011, Pages 363-369

  Koeppen, Michael ^a,b   Eckle, Tobias ^a   Eltzschig, Holger K ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

A2BAR; adenosine receptor; erythropoietin; hypoxia inducible factor; prolyl hydroxylase

Indexed keywords

ERYTHROPOIETIN; HEAT SHOCK PROTEIN 90 INHIBITOR; HYPOXIA INDUCIBLE FACTOR; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE;

ACUTE HEART INFARCTION; ACUTE KIDNEY FAILURE; ACUTE LUNG INJURY; DISEASE ASSOCIATION; DRUG TARGETING; GENE EXPRESSION; HEART MUSCLE ISCHEMIA; HYPOXIA; INFLAMMATION; OXYGEN CONSUMPTION; PATIENT CARE; PERIOPERATIVE PERIOD; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL HYPOXIA; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INFLAMMATION; PROCOLLAGEN-PROLINE DIOXYGENASE; SIGNAL TRANSDUCTION;

EID: 79960700105     PISSN: 09527907     EISSN: 14736500     Source Type: Journal    
DOI: 10.1097/ACO.0b013e32834873fd     Document Type: Review

References (88)

1. Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med 2011 364: 656-665.
2. Eltzschig HK. Adenosine: an old drug newly discovered. Anesthesiology 2009; 111:904-915.
3. Eltzschig HK. Targeting hypoxia-induced inflammation. Anesthesiology 2011; 114:239-242.
4. Andrade CF, Kaneda H, Der S, et al. Toll-like receptor and cytokine gene expression in the early phase of human lung transplantation. J Heart Lung Transplant 2006; 25:1317-1323. (Pubitemid 44767731)
5. De Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 2002; 165:211-215. (Pubitemid 34084460)
6. Del Rizzo DF, Menkis AH, Pflugfelder PW, et al. The role of donor age and ischemic time on survival following orthotopic heart transplantation. J Heart Lung Transplant 1999; 18:310-319. (Pubitemid 29205266)
7. Thabut G, Mal H, Cerrina J, et al. Graft ischemic time and outcome of lung transplantation: a multicenter analysis. Am J Respir Crit Care Med 2005; 171:786-791. (Pubitemid 40471151)
8. Eckle T, Kohler D, Lehmann R, et al. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 2008; 118:166-175.
9. Bauerle JD, Grenz A, Kim JH, et al. Adenosine generation and signaling during acute kidney injury. J Am Soc Nephrol 2011; 22:14-20.
10. Grenz A, Dalton HJ, Bauerle J, et al. Partial netrin-1 deficiency aggravates acute kidney injury. PLoS One (in press).
11. Grenz A, Eckle T, Zhang H, et al. Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice. Am J Physiol Renal Physiol 2007; 292:F475-F485. (Pubitemid 46105286)
12. Grenz A, Osswald H, Eckle T, et al. The reno-vascular A2B adenosine receptor protects the kidney from ischemia. PLoS Med 2008; 5:e137.
13. Grenz A, Zhang H, Eckle T, et al. Protective role of ecto-50-nucleotidase (CD73) in renal ischemia. J Am Soc Nephrol 2007; 18:833-845. (Pubitemid 46434500)
14. Grenz A, Zhang H, Weingart J, et al. Lack of effect of extracellular adenosine generation and signalling on renal erythropoietin secretion during hypoxia. Am J Physiol Renal Physiol 2007, 293:F1501-F1511. (Pubitemid 350085985)
15. Eckle T, Grenz A, Laucher S, et al. A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice. J Clin Invest 2008; 118:3301-3315.
16. Eckle T, Faigle M, Grenz A, et al. A2B adenosine receptor dampens hypoxiainduced vascular leak. Blood 2008; 111:2024-2035. (Pubitemid 351451513)
17. Eckle T, Fullbier L, Wehrmann M, et al. Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury. J Immunol 2007; 178:8127-8137. (Pubitemid 46898085)
18. Eckle T, Koeppen M, Eltzschig HK. Role of extracellular adenosine in acute lung injury. Physiology (Bethesda) 2009; 24:298-306.
19. Hartmann G, Tschop M, Fischer R, et al. High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine 2000; 12:246-252. (Pubitemid 30449882)
20. Rosenberger P, Schwab JM, Mirakaj V, et al. Hypoxia-inducible factordependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol 2009; 10:195-202.
21. Eltzschig HK, Abdulla P, Hoffman E, et al. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. J Exp Med 2005; 202:1493-1505. (Pubitemid 41746596)
22. Eltzschig HK, Ibla JC, Furuta GT, et al. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J Exp Med 2003; 198:783-796. (Pubitemid 37087777)
23. Eltzschig HK, Thompson LF, Karhausen J, et al. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood 2004; 104:3986-3992. (Pubitemid 39620148)
24. Kruger B, Krick S, Dhillon N, et al. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci U S A 2009; 106:3390-3395.
25. Kim M, Park SW, Pitson SM, et al. Isoflurane protects human kidney proximal tubule cells against necrosis via sphingosine kinase and sphingosine-1- phosphate generation. Am J Nephrol 2010; 31:353-362.
26. Park SW, Kim M, Brown KM, et al. Paneth cell-derived IL-17A causes multiorgan dysfunction after hepatic ischemia and reperfusion injury. Hepatology 2011; 53:1662-1675.
27. Hart ML, Jacobi B, Schittenhelm J, et al. Cutting Edge: A2B Adenosine receptor signaling provides potent protection during intestinal ischemia/ reperfusion injury. J Immunol 2009; 182:3965-3968.
28. Hart ML, Gorzolla IC, Schittenhelm J, et al. SP1-dependent induction of CD39 facilitates hepatic ischemic preconditioning. J Immunol 2010; 184:4017-4024.
29. Hart ML, Grenz A, Gorzolla IC, et al. Hypoxia-inducible factor-1alpha-dependent protection from intestinal ischemia/reperfusion injury involves ecto-50 - nucleotidase (CD73) and the A2B adenosine receptor. J Immunol 2011 186: 4367-4374.
30. Hart ML, Henn M, Kohler D, et al. Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury. FASEB J 2008; 22:2784-2797.
31. Hart ML, Jacobi B, Schittenhelm J, et al. Cutting edge: A2B adenosine receptor signaling provides potent protection during intestinal ischemia/ reperfusion injury. J Immunol 2009; 182:3965-3968.
32. Hart ML, Much C, Gorzolla IC, et al. Extracellular adenosine production by ecto-50-nucleotidase protects during murine hepatic ischemic preconditioning. Gastroenterology 2008; 135:1739 e3-1750 e3.
33. Giatromanolaki A, Sivridis E, Maltezos E, et al. Hypoxia inducible factor 1alpha and 2alpha overexpression in inflammatory bowel disease. J Clin Pathol 2003; 56:209-213. (Pubitemid 36308037)
34. Colgan SP, Taylor CT. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol 2010; 7:281-287.
35. Taylor CT, Colgan SP. Hypoxia and gastrointestinal disease. J Mol Med 2007; 85:1295-1300. (Pubitemid 50004090)
36. Taylor CT. Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation. J Physiol 2008; 586:4055-4059.
37. Eltzschig HK, Eckle T, Mager A, et al. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res 2006; 99:1100-1108. (Pubitemid 44729934)
38. Eltzschig HK, Macmanus CF, Colgan SP. Neutrophils as sources of extracellular nucleotides: functional consequences at the vascular interface. Trends Cardiovasc Med 2008; 18:103-107. (Pubitemid 351626607)
39. Faigle M, Seessle J, Zug S, et al. ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia. PLoS One 2008; 3:e2801.
40. Kohler D, Eckle T, Faigle M, et al. CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/ reperfusion injury. Circulation 2007; 116:1784-1794. (Pubitemid 350287103)
41. Robinson A, Keely S, Karhausen J, et al. Mucosal protection by hypoxiainducible factor prolyl hydroxylase inhibition. Gastroenterology 2008; 134:145-155. (Pubitemid 350309309)
42. Cummins EP, Seeballuck F, Keely SJ, et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 2008; 134:156-165.
43. Aherne CM, Kewley EM, Eltzschig HK. The resurgence of A2B adenosine receptor signaling. Biochim Biophys Acta 2011; 1808:1329-1339
44. Eckle T, Fullbier L,Grenz A, et al. Usefulness of pressure-controlled ventilation at high inspiratory pressures to induce acute lung injury in mice. Am J Physiol Lung Cell Mol Physiol 2008; 295:L718-L724.
45. Eltzschig HK, Faigle M, Knapp S, et al. Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood 2006; 108:1602-1610. (Pubitemid 44316128)
46. Kong T, Westerman KA, Faigle M, et al. HIF-dependent induction of adenosine A2B receptor in hypoxia. FASEB J 2006; 20:2242-2250. (Pubitemid 44953854)
47. Loffler M, Morote-Garcia JC, Eltzschig SA, et al. Physiological roles of vascular nucleoside transporters. Arterioscler Thromb Vasc Biol 2007; 27:1004-1013. (Pubitemid 46641985)
48. Morote-Garcia JC, Rosenberger P, Kuhlicke J, et al. HIF-1-dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak. Blood 2008; 111:5571-5580.
49. Morote-Garcia JC, Rosenberger P, Nivillac NM, et al. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology 2009; 136:607-618.
50. Reutershan J, Vollmer I, Stark S, et al. Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. FASEB J 2009; 23:473-482.
51. Semenza GL, Roth PH, Fang HM, et al. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 1994; 269:23757-23763. (Pubitemid 24293585)
52. 2 tension. Proc Natl Acad Sci U S A 1995; 92:5510-5514.
53. Semenza GL. Life with oxygen. Science 2007; 318:62-64. (Pubitemid 47538005)
54. Kong T, Eltzschig HK, Karhausen J, et al. Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of {beta}2 integrin gene expression. Proc Natl Acad Sci U S A 2004; 101:10440-10445. (Pubitemid 38924944)
55. Synnestvedt K, Furuta GT, Comerford KM, et al. Ecto-50-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest 2002; 110:993-1002.
56. Kuhlicke J, Frick JS, Morote-Garcia JC, et al. Hypoxia inducible factor (HIF)-1 coordinates induction of toll-like receptors TLR2 and TLR6 during hypoxia. PLoS One 2007; 2:e1364.
57. Zheng W, Kuhlicke J, Jackel K, et al. Hypoxia inducible factor-1 (HIF-1)- mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium. FASEB J 2009; 23:204-213.
58. 2- regulated gene expression. FASEB J 2002; 16:1151-1162. (Pubitemid 34815403)
59. Holmquist-Mengelbier L, Fredlund E, Lofstedt T, et al. Recruitment of HIF- 1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 2006; 10:413-423. (Pubitemid 44693470)
60. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004; 5:343-354. (Pubitemid 38579472)
61. Rankin EB, Biju MP, Liu Q, et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest 2007; 117:1068-1077. (Pubitemid 46556763)
62. Ratcliffe PJ. HIF-1 and HIF-2: working alone or together in hypoxia? J Clin Invest 2007; 117:862-865. (Pubitemid 46556739)
63. Hu CJ, Wang LY, Chodosh LA, et al. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 2003; 23:9361-9374. (Pubitemid 37499822)
64. Brusselmans K, Compernolle V, Tjwa M, et al. Heterozygous deficiency of hypoxia-inducible factor-2{alpha} protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 2003; 111:1519-1527. (Pubitemid 38063284)
65. Compernolle V, Brusselmans K, Acker T, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 2002; 8:702-710. (Pubitemid 34778723)
66. Kaelin WG. Proline hydroxylation and gene expression. Annu Rev Biochem 2005; 74:115-128.
67. Kaelin WG Jr, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 2008; 30:393-402. (Pubitemid 351681994)
68. Aragones J, Fraisl P, Baes M, et al. Oxygen sensors at the crossroad of metabolism. Cell Metab 2009; 9:11-22.
69. Fraisl P, Aragones J, Carmeliet P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov 2009; 8:139-152.
70. Kaelin WG. Von Hippel-Lindau disease. Annu Rev Pathol 2007; 2:145-173.
71. 2 sensing and cancer. Nat Rev Cancer 2008; 8:865-873.
72. Dayan F, Roux D, Brahimi-Horn MC, et al. The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1alpha. Cancer Res 2006; 66:3688-3698.
73. Kong X, Lin Z, Liang D, et al. Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha. Mol Cell Biol 2006; 26:2019-2028. (Pubitemid 43346906)
74. Karhausen J, Furuta GT, Tomaszewski JE, et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest 2004; 114:1098-1106. (Pubitemid 39578699)
75. Eckle T, Grenz A, Kohler D, et al. Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. Am J Physiol Heart Circ Physiol 2006; 291:H2533-H2540.
76. Eckle T, Krahn T, Grenz A, et al. Cardioprotection by ecto-50-nucleotidase (CD73) and A2B adenosine receptors. Circulation 2007; 115:1581-1590. (Pubitemid 46648643)
77. Grenz A, Homann D, Eltzschig HK. Extracellular adenosine - a 'safety signal' that dampens hypoxia-induced inflammation during ischemia. Antioxid Redox Signal 2011. [Epub ahead of print]
78. Grenz A, Zhang H, Hermes M, et al. Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury. FASEB J 2007; 21:2863-2873. (Pubitemid 47372753)
79. Chen H, Yang D, Carroll SH, et al. Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury. Exp Hematol 2009; 37:533-538.
80. Csoka B, Nemeth ZH, Rosenberger P, et al. A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation. J Immunol 2010; 185:542-550.
81. Eltzschig HK, Rivera-Nieves J, Colgan SP. Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation. Expert Opin Ther Targets 2009; 13:1267-1277.
82. Frick JS, MacManus CF, Scully M, et al. Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis. J Immunol 2009; 182:4957-4964.
83. Schingnitz U, Hartmann K, Macmanus CF, et al. Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury. J Immunol 2010; 184:5271-5279.
84. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342:1334-1349. (Pubitemid 30408719)
85. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353:1685-1693. (Pubitemid 41464707)
86. Licker M, de Perrot M, Spiliopoulos A, et al. Risk factors for acute lung injury after thoracic surgery for lung cancer. Anesth Analg 2003; 97:1558-1565. (Pubitemid 37475100)
87. Milot J, Perron J, Lacasse Y, et al. Incidence and predictors of ARDS after cardiac surgery. Chest 2001; 119:884-888. (Pubitemid 32197663)
88. Shorr AF, Abbott KC, Agadoa LY. Acute respiratory distress syndrome after kidney transplantation: epidemiology, risk factors, and outcomes. Crit Care Med 2003; 31:1325-1330. (Pubitemid 36583839)