Much ado about adenosine: Adenosine synthesis and function in regulatory T cell biology

Journal of Immunology

Volumn 185, Issue 4, 2010, Pages 1993-1998

  Ernst, Peter B ^a,b   Garrison, James C ^b   Thompson, Linda F ^c  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ADENOSINE RECEPTOR; CYCLIC AMP; CYTOKINE;

CELL FUNCTION; INFLAMMATORY CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REGULATORY T LYMPHOCYTE; SHORT SURVEY; ANIMAL; ANTIGEN PRESENTING CELL; BIOLOGICAL MODEL; BIOSYNTHESIS; HELPER CELL; HUMAN; IMMUNOLOGY; METABOLISM; REVIEW;

ADENOSINE; ANIMALS; ANTIGEN-PRESENTING CELLS; CYCLIC AMP; CYTOKINES; HUMANS; MODELS, IMMUNOLOGICAL; RECEPTORS, PURINERGIC P1; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY;

EID: 77956896083     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1000108     Document Type: Short Survey

References (89)

1. Haskó, G., J. Linden, B. Cronstein, and P. Pacher. 2008. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat. Rev. Drug Discov. 7: 759-770.
2. Linden, J. 2006. New insights into the regulation of inflammation by adenosine. J. Clin. Invest. 116: 1835-1837.
3. Lukashev, D. E., P. T. Smith, C. C. Caldwell, A. Ohta, S. G. Apasov, and M. V. Sitkovsky. 2003. Analysis of A2a receptor-deficient mice reveals no significant compensatory increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid organs. Biochem. Pharmacol. 65: 2081-2090.
4. Sitkovsky, M. V., D. Lukashev, S. Apasov, H. Kojima, M. Koshiba, C. Caldwell, A. Ohta, and M. Thiel. 2004. Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu. Rev. Immunol. 22: 657-682.
5. Wakamiya, M., M. R. Blackburn, R. Jurecic, M. J. McArthur, R. S. Geske, J. Cartwright, Jr., K. Mitani, S. Vaishnav, J. W. Belmont, R. E. Kellems, et al. 1995. Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice. Proc. Natl. Acad. Sci. USA 92: 3673-3677.
6. Deaglio, S., K. M. Dwyer, W. Gao, D. Friedman, A. Usheva, A. Erat, J. F. Chen, K. Enjyoji, J. Linden, M. Oukka, et al. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204: 1257-1265.
7. Thompson, L. F., H. K. Eltzschig, J. C. Ibla, C. J. Van De Wiele, R. Resta, J. C. Morote-Garcia, and S. P. Colgan. 2004. Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J. Exp. Med. 200: 1395-1405.
8. Castrop, H., Y. Huang, S. Hashimoto, D. Mizel, P. Hansen, F. Theilig, S. Bachmann, C. Deng, J. Briggs, and J. Schnermann. 2004. Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73- deficient mice. J. Clin. Invest. 114: 634-642.
9. Koszalka, P., B. Ozüyaman, Y. Huo, A. Zernecke, U. Flögel, N. Braun, A. Buchheiser, U. K. Decking, M. L. Smith, J. Sévigny, et al. 2004. Targeted disruption of cd73/ecto-5′-nucleotidase alters thromboregulation and augments vascular inflammatory response. Circ. Res. 95: 814-821.
10. Alam, M. S., C. C. Kurtz, R. M. Rowlett, B. K. Reuter, E. Wiznerowicz, S. Das, J. Linden, S. E. Crowe, and P. B. Ernst. 2009. CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice. J. Infect. Dis. 199: 494-504.
11. Naganuma, M., E. B. Wiznerowicz, C. M. Lappas, J. Linden, M. T. Worthington, and P. B. Ernst. 2006. Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J. Immunol. 177: 2765-2769.
12. Kobie, J. J., P. R. Shah, L. Yang, J. A. Rebhahn, D. J. Fowell, and T. R. Mosmann. 2006. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5′-adenosine monophosphate to adenosine. J. Immunol. 177: 6780-6786.
13. Borsellino, G., M. Kleinewietfeld, D. Di Mitri, A. Sternjak, A. Diamantini, R. Giometto, S. Höpner, D. Centonze, G. Bernardi, M. L. Dell'Acqua, et al. 2007. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110: 1225-1232. (Pubitemid 47281420)
14. Clark, R. A., S. J. Huang, G. F. Murphy, I. G. Mollet, D. Hijnen, M. Muthukuru, C. F. Schanbacher, V. Edwards, D. M. Miller, J. E. Kim, et al. 2008. Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells. J. Exp. Med. 205: 2221-2234.
15. Vukmanovic-Stejic, M., E. Agius, N. Booth, P. J. Dunne, K. E. Lacy, J. R. Reed, T. O. Sobande, S. Kissane, M. Salmon, M. H. Rustin, and A. N. Akbar. 2008. The kinetics of CD4+Foxp3+ T cell accumulation during a human cutaneous antigen-specific memory response in vivo. J. Clin. Invest. 118: 3639-3650.
16. Ring, S., S. J. Oliver, B. N. Cronstein, A. H. Enk, and K. Mahnke. 2009. CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. J. Allergy Clin. Immunol. 123: 1287-1296, e2.
17. Gavin, M. A., J. P. Rasmussen, J. D. Fontenot, V. Vasta, V. C. Manganiello, J. A. Beavo, and A. Y. Rudensky. 2007. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445: 771-775.
18. Alyanakian, M. A., S. You, D. Damotte, C. Gouarin, A. Esling, C. Garcia, S. Havouis, L. Chatenoud, and J. F. Bach. 2003. Diversity of regulatory CD4+ T cells controlling distinct organ-specific autoimmune diseases. Proc. Natl. Acad. Sci. USA 100: 15806-15811.
19. Fletcher, J. M., R. Lonergan, L. Costelloe, K. Kinsella, B. Moran, C. O'Farrelly, N. Tubridy, and K. H. Mills. 2009. CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J. Immunol. 183: 7602-7610.
20. + T cells. Immunity 1: 553-562.
21. -/-) mice delays clearance of gastric Helicobacter infection and decreases the Th1 immune response to Helicobacter. J. Immunol. 170: 3782-3789.
22. Rad, R., L. Brenner, S. Bauer, S. Schwendy, L. Layland, C. P. da Costa, W. Reindl, A. Dossumbekova, M. Friedrich, D. Saur, et al. 2006. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology 131: 525-537.
23. Harris, P. R., S. W. Wright, C. Serrano, F. Riera, I. Duarte, J. Torres, A. Peña, A. Rollán, P. Viviani, E. Guiraldes, et al. 2008. Helicobacter pylori gastritis in children is associated with a regulatory T-cell response. Gastroenterology 134: 491-499.
24. Alam, M. S., C. C. Kurtz, J. M. Wilson, B. R. Burnette, E. B. Wiznerowicz, W. G. Ross, J. M. Rieger, R. A. Figler, J. Linden, S. E. Crowe, and P. B. Ernst. 2009. A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence. Mucosal Immunol. 2: 232-242.
25. Ernst, P. B., D. A. Peura, and S. E. Crowe. 2006. The translation of Helicobacter pylori basic research to patient care. Gastroenterology 130: 188-206, quiz 212-213.
26. Friedman, D. J., B. M. Künzli, Y. I. A-Rahim, J. Sevigny, P. O. Berberat, K. Enjyoji, E. Csizmadia, H. Friess, and S. C. Robson. 2009. From the Cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc. Natl. Acad. Sci. USA 106: 16788-16793.
27. Ohta, A., and M. Sitkovsky. 2001. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414: 916-920.
28. Lappas, C. M., J. M. Rieger, and J. Linden. 2005. A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J. Immunol. 174: 1073-1080.
29. Koshiba, M., D. L. Rosin, N. Hayashi, J. Linden, and M. V. Sitkovsky. 1999. Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies. Mol. Pharmacol. 55: 614-624.
30. Huang, S., S. Apasov, M. Koshiba, and M. Sitkovsky. 1997. Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90: 1600-1610. (Pubitemid 27355433)
31. Ben Addi, A., A. Lefort, X. Hua, F. Libert, D. Communi, C. Ledent, P. Macours, S. L. Tilley, J. M. Boeynaems, and B. Robaye. 2008. Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A(2B) receptor. Eur. J. Immunol. 38: 1610-1620.
32. Németh, Z. H., C. S. Lutz, B. Csóka, E. A. Deitch, S. J. Leibovich, W. C. Gause, M. Tone, P. Pacher, E. S. Vizi, and G. Haskó. 2005. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J. Immunol. 175: 8260-8270.
33. Haskó, G., D. G. Kuhel, J. F. Chen, M. A. Schwarzschild, E. A. Deitch, J. G. Mabley, A. Marton, and C. Szabó. 2000. Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 14: 2065-2074.
34. Haskó, G., C. Szabó, Z. H. Németh, V. Kvetan, S. M. Pastores, and E. S. Vizi. 1996. Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J. Immunol. 157: 4634-4640.
35. Panther, E., M. Idzko, Y. Herouy, H. Rheinen, P. J. Gebicke-Haerter, U. Mrowietz, S. Dichmann, and J. Norgauer. 2001. Expression and function of adenosine receptors in human dendritic cells. FASEB J. 15: 1963-1970.
36. Murphree, L. J., G. W. Sullivan, M. A. Marshall, and J. Linden. 2005. Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-kappaB in A(2A) adenosine receptor induction. Biochem. J. 391: 575-580.
37. Wilson, J. M., W. G. Ross, O. N. Agbai, R. Frazier, R. A. Figler, J. Rieger, J. Linden, and P. B. Ernst. 2009. The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. J. Immunol. 182: 4616-4623.
38. Fotheringham, J. A., M. B. Mayne, J. A. Grant, and J. D. Geiger. 2004. Activation of adenosine receptors inhibits tumor necrosis factor-alpha release by decreasing TNF-alpha mRNA stability and p38 activity. Eur. J. Pharmacol. 497: 87-95.
39. Novitskiy, S. V., S. Ryzhov, R. Zaynagetdinov, A. E. Goldstein, Y. Huang, O. Y. Tikhomirov, M. R. Blackburn, I. Biaggioni, D. P. Carbone, I. Feoktistov, and M. M. Dikov. 2008. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 112: 1822-1831.
40. Onishi, Y., Z. Fehervari, T. Yamaguchi, and S. Sakaguchi. 2008. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl. Acad. Sci. USA 105: 10113-10118.
41. Wing, K., Y. Onishi, P. Prieto-Martin, T. Yamaguchi, M. Miyara, Z. Fehervari, T. Nomura, and S. Sakaguchi. 2008. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322: 271-275.
42. Zarek, P. E., C. T. Huang, E. R. Lutz, J. Kowalski, M. R. Horton, J. Linden, C. G. Drake, and J. D. Powell. 2008. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111: 251-259.
43. Bopp, T., C. Becker, M. Klein, S. Klein-Hessling, A. Palmetshofer, E. Serfling, V. Heib, M. Becker, J. Kubach, S. Schmitt, et al. 2007. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J. Exp. Med. 204: 1303-1310.
44. Bopp, T., N. Dehzad, S. Reuter, M. Klein, N. Ullrich, M. Stassen, H. Schild, R. Buhl, E. Schmitt, and C. Taube. 2009. Inhibition of cAMP degradation improves regulatory T cell-mediated suppression. J. Immunol. 182: 4017-4024.
45. Huang, B., J. Zhao, Z. Lei, S. Shen, D. Li, G. X. Shen, G. M. Zhang, and Z. H. Feng. 2009. miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 10: 180-185.
46. Nakamura, K., A. Kitani, I. Fuss, A. Pedersen, N. Harada, H. Nawata, and W. Strober. 2004. TGF-beta 1 plays an important role in themechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J. Immunol. 172: 834-842. (Pubitemid 38113739)
47. Collison, L. W., C. J. Workman, T. T. Kuo, K. Boyd, Y. Wang, K. M. Vignali, R. Cross, D. Sehy, R. S. Blumberg, and D. A. Vignali. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450: 566-569.
48. Workman, C. J., and D. A. Vignali. 2005. Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J. Immunol. 174: 688-695.
49. Haskó, G., and B. N. Cronstein. 2004. Adenosine: an endogenous regulator of innate immunity. Trends Immunol. 25: 33-39.
50. Seybold, J., R. Newton, L. Wright, P. A. Finney, N. Suttorp, P. J. Barnes, I. M. Adcock, and M. A. Giembycz. 1998. Induction of phosphodiesterases 3B, 4A4, 4D1, 4D2, and 4D3 in Jurkat T-cells and in human peripheral blood T-lymphocytes by 8-bromo-cAMP and Gs-coupled receptor agonists. Potential role in beta2-adrenoreceptor desensitization. J. Biol. Chem. 273: 20575-20588.
51. Conti, M., and J. Beavo. 2007. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu. Rev. Biochem. 76: 481-511.
52. Zhou, W., and R. König. 2003. T cell receptor-independent CD4 signalling: CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP. Cell. Signal. 15: 751-762.
53. Denning, T. L., H. Qi, R. König, K. G. Scott, M. Naganuma, and P. B. Ernst. 2003. CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC. J. Immunol. 171: 2279-2286.
54. Bjørgo, E., and K. Taskén. 2006. Role of cAMP phosphodiesterase 4 in regulation of T-cell function. Crit. Rev. Immunol. 26: 443-451.
55. Staples, K. J., M. Bergmann, K. Tomita, M. D. Houslay, I. McPhee, P. J. Barnes, M. A. Giembycz, and R. Newton. 2001. Adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent inhibition of IL-5 from human T lymphocytes is not mediated by the cAMP-dependent protein kinase A. J. Immunol. 167: 2074-2080.
56. Taylor, S. S., C. Kim, C. Y. Cheng, S. H. Brown, J. Wu, and N. Kannan. 2008. Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug design. Biochim. Biophys. Acta 1784: 16-26.
57. Carnegie, G. K., C. K. Means, and J. D. Scott. 2009. A-kinase anchoring proteins: from protein complexes to physiology and disease. IUBMB Life 61: 394-406.
58. Cheng, X., Z. Ji, T. Tsalkova, and F. Mei. 2008. Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim. Biophys. Sin. (Shanghai) 40: 651-662.
59. Sullivan, G. W., J. M. Rieger, W. M. Scheld, T. L. Macdonald, and J. Linden. 2001. Cyclic AMP-dependent inhibition of human neutrophil oxidative activity by substituted 2-propynylcyclohexyl adenosine A(2A) receptor agonists. Br. J. Pharmacol. 132: 1017-1026.
60. Sands, W. A., and T. M. Palmer. 2008. Regulating gene transcription in response to cyclic AMP elevation. Cell. Signal. 20: 460-466.
61. Kim, H. P., and W. J. Leonard. 2007. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 204: 1543-1551.
62. Hughes-Fulford, M., E. Sugano, T. Schopper, C. F. Li, J. B. Boonyaratanakornkit, and A. Cogoli. 2005. Early immune response and regulation of IL-2 receptor subunits. Cell. Signal. 17: 1111-1124.
63. Claveau, D., S. L. Chen, S. O'Keefe, D. M. Zaller, A. Styhler, S. Liu, Z. Huang, D. W. Nicholson, and J. A. Mancini. 2004. Preferential inhibition of T helper 1, but not T helper 2, cytokines in vitro by L-826,141 [4-[2-(3,4-Bisdifluromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2- hydroxypropan-2-yl)-phenyl]-ethyl]3-methylpyridine-1-oxide], a potent and selective phosphodiesterase 4 inhibitor. J. Pharmacol. Exp. Ther. 310: 752-760.
64. Roscioni, S. S., C. R. Elzinga, and M. Schmidt. 2008. Epac: effectors and biological functions. Naunyn Schmiedebergs Arch. Pharmacol. 377: 345-357.
65. Sands, W. A., H. D. Woolson, G. R. Milne, C. Rutherford, and T. M. Palmer. 2006. Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol. Cell. Biol. 26: 6333-6346.
66. Dimitriou, I. D., L. Clemenza, A. J. Scotter, G. Chen, F. M. Guerra, and R. Rottapel. 2008. Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. Immunol. Rev. 224: 265-283.
67. Csóka, B., Z. H. Németh, L. Virág, P. Gergely, S. J. Leibovich, P. Pacher, C. X. Sun, M. R. Blackburn, E. S. Vizi, E. A. Deitch, and G. Haskó. 2007. A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood 110: 2685-2695.
68. Hubbard, K. B., and J. R. Hepler. 2006. Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. Cell. Signal. 18: 135-150.
69. Lycke, N. 1997. The mechanism of cholera toxin adjuvanticity. Res. Immunol. 148: 504-520.
70. Németh, Z. H., S. J. Leibovich, E. A. Deitch, B. Sperlágh, L. Virág, E. S. Vizi, C. Szabó, and G. Haskó. 2003. Adenosine stimulates CREB activation in macrophages via a p38 MAPK-mediated mechanism. Biochem. Biophys. Res. Commun. 312: 883-888.
71. Sun, Y., F. Wu, F. Sun, and P. Huang. 2008. Adenosine promotes IL-6 release in airway epithelia. J. Immunol. 180: 4173-4181.
72. Hudmon, A., and H. Schulman. 2002. Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II. Biochem. J. 364: 593-611. (Pubitemid 34680833)
73. Tan, S. L., and P. J. Parker. 2003. Emerging and diverse roles of protein kinase C in immune cell signalling. Biochem. J. 376: 545-552.
74. Mills, J. H., L. F. Thompson, C. Mueller, A. T. Waickman, S. Jalkanen, J. Niemela, L. Airas, and M. S. Bynoe. 2008. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 105: 9325-9330.
75. Chen, W., W. Jin, N. Hardegen, K. J. Lei, L. Li, N. Marinos, G. McGrady, and S. M. Wahl. 2003. Conversion of peripheral CD4+CD25- naive T cells to CD4 +CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 198: 1875-1886.
76. Dardalhon, V., A. Awasthi, H. Kwon, G. Galileos, W. Gao, R. A. Sobel, M. Mitsdoerffer, T. B. Strom, W. Elyaman, I. C. Ho, et al. 2008. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat. Immunol. 9: 1347-1355.
77. Zhou, L., I. I. Ivanov, R. Spolski, R. Min, K. Shenderov, T. Egawa, D. E. Levy, W. J. Leonard, and D. R. Littman. 2007. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8: 967-974.
78. Kolachala, V. L., M. Vijay-Kumar, G. Dalmasso, D. Yang, J. Linden, L. Wang, A. Gewirtz, K. Ravid, D. Merlin, and S. V. Sitaraman. 2008. A2B adenosine receptor gene deletion attenuates murine colitis. Gastroenterology 135: 861-870.
79. Frick, J. S., C. F. MacManus, M. Scully, L. E. Glover, H. K. Eltzschig, and S. P. Colgan. 2009. Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis. J. Immunol. 182: 4957-4964.
80. Sun, C. X., H. Zhong, A. Mohsenin, E. Morschl, J. L. Chunn, J. G. Molina, L. Belardinelli, D. Zeng, and M. R. Blackburn. 2006. Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury. J. Clin. Invest. 116: 2173-2182.
81. Che, J., E. S. Chan, and B. N. Cronstein. 2007. Adenosine A2A receptor occupancy stimulates collagen expression by hepatic stellate cells via pathways involving protein kinase A, Src, and extracellular signal-regulated kinases 1/2 signaling cascade or p38 mitogen-activated protein kinase signaling pathway. Mol. Pharmacol. 72: 1626-1636.
82. Thiel, M., C. C. Caldwell, and M. V. Sitkovsky. 2003. The critical role of adenosine A2A receptors in downregulation of inflammation and immunity in the pathogenesis of infectious diseases. Microbes Infect. 5: 515-526.
83. Lukashev, D., M. Sitkovsky, and A. Ohta. 2007. From "Hellstrom Paradox" to antiadenosinergic cancer immunotherapy. Purinergic Signal. 3: 129-134.
84. Ohta, A., E. Gorelik, S. J. Prasad, F. Ronchese, D. Lukashev, M. K. Wong, X. Huang, S. Caldwell, K. Liu, P. Smith, et al. 2006. A2A adenosine receptor protects tumors from antitumor T cells. Proc. Natl. Acad. Sci. USA 103: 13132-13137.
85. Jin, D., J. Fan, L. Wang, L. F. Thompson, A. Liu, B. J. Daniel, T. Shin, T. J. Curiel, and B. Zhang. 2010. CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res. 70: 2245-2255.
86. Zhou, X., X. Zhi, P. Zhou, S. Chen, F. Zhao, Z. Shao, Z. Ou, and L. Yin. 2007. Effects of ecto-59-nucleotidase on human breast cancer cell growth in vitro and in vivo. Oncol. Rep. 17: 1341-1346.
87. Stagg, J., U. Divisekera, N. McLaughlin, J. Sharkey, S. Pommey, D. Denoyer, K. M. Dwyer, and M. J. Smyth. 2010. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 107: 1547-1552.
88. Németh, Z. H., B. Csóka, J. Wilmanski, D. Xu, Q. Lu, C. Ledent, E. A. Deitch, P. Pacher, Z. Spolarics, and G. Haskó. 2006. Adenosine A2A receptor inactivation increases survival in polymicrobial sepsis. J. Immunol. 176: 5616-5626.
89. Sullivan, G. W., G. Fang, J. Linden, and W. M. Scheld. 2004. A2A adenosine receptor activation improves survival in mouse models of endotoxemia and sepsis. J. Infect. Dis. 189: 1897-1904.