The pleiotropic effects of erythropoietin in infection and inflammation

Microbes and Infection

Volumn 14, Issue 3, 2012, Pages 238-246

  Nairz, Manfred ^a   Sonnweber, Thomas ^a   Schroll, Andrea ^a   Theurl, Igor ^a   Weiss, Günter ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Anemia; Erythropoietin; Infection; Innate immunity; Iron; Salmonella

Indexed keywords

RECOMBINANT ERYTHROPOIETIN;

APLASTIC ANEMIA; AUTOIMMUNITY; ESCHERICHIA COLI INFECTION; IMMUNOMODULATION; INFECTION; INFLAMMATION; MACROPHAGE FUNCTION; NAGANA; NONHUMAN; PLASMODIUM BERGHEI INFECTION; PLASMODIUM CHABAUDI INFECTION; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN FUNCTION; SALMONELLOSIS; SHORT SURVEY; SIGNAL TRANSDUCTION;

ANEMIA, HEMOLYTIC; ANIMALS; CELL HYPOXIA; ERYTHROPOIESIS; ERYTHROPOIETIN; GENETIC PLEIOTROPY; HOST-PATHOGEN INTERACTIONS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INFLAMMATION; MACROPHAGES; MICE; NF-KAPPA B; SALMONELLA; SALMONELLA INFECTIONS; SIGNAL TRANSDUCTION;

ANIMALIA; SALMONELLA;

EID: 84856317888     PISSN: 12864579     EISSN: 1769714X     Source Type: Journal    
DOI: 10.1016/j.micinf.2011.10.005     Document Type: Short Survey

References (82)

1. De Maria R., Zeuner A., Eramo A., Domenichelli C., Bonci D., Grignani F., Srinivasula S.M., Alnemri E.S., Testa U., Peschle C. Negative regulation of erythropoiesis by caspase-mediated cleavage of GATA-1. Nature 1999, 401:489-493.
2. Pevny L., Simon M.C., Robertson E., Klein W.H., Tsai S.F., D'Agati V., Orkin S.H., Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 1991, 349:257-260.
3. Liu Y., Pop R., Sadegh C., Brugnara C., Haase V.H., Socolovsky M. Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response invivo. Blood 2006, 108:123-133.
4. Haase V.H. Hypoxic regulation of erythropoiesis and iron metabolism. Am. J. Physiol. Ren. Physiol. 2010, 299:F1-13.
5. Eckardt K.U., Kurtz A. Regulation of erythropoietin production. Eur. J. Clin. Invest. 2005, 35(Suppl 3):13-19.
6. Boutin A.T., Weidemann A., Fu Z., Mesropian L., Gradin K., Jamora C., Wiesener M., Eckardt K.U., Koch C.J., Ellies L.G., Haddad G., Haase V.H., Simon M.C., Poellinger L., Powell F.L., Johnson R.S. Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell 2008, 133:223-234.
7. Jelkmann W. Erythropoietin after a century of research: younger than ever. Eur. J. Haematol. 2007, 78:183-205.
8. La Ferla K., Reimann C., Jelkmann W., Hellwig-Burgel T. Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. FASEB J. 2002, 16:1811-1813.
9. Weiss G., Goodnough L.T. Anemia of chronic disease. N. Engl. J. Med. 2005, 352:1011-1023.
10. Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J. Interferon Cytokine Res. 1998, 18:555-559.
11. Ramadori P., Ahmad G., Ramadori G. Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6. Lab. Invest. 2010, 90:1306-1324.
12. Jantsch J., Chakravortty D., Turza N., Prechtel A.T., Buchholz B., Gerlach R.G., Volke M., Glasner J., Warnecke C., Wiesener M.S., Eckardt K.U., Steinkasserer A., Hensel M., Willam C. Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide-induced dendritic cell activation and function. J. Immunol. 2008, 180:4697-4705.
13. Peyssonnaux C., Datta V., Cramer T., Doedens A., Theodorakis E.A., Gallo R.L., Hurtado-Ziola N., Nizet V., Johnson R.S. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J. Clin. Invest. 2005, 115:1806-1815.
14. Rius J., Guma M., Schachtrup C., Akassoglou K., Zinkernagel A.S., Nizet V., Johnson R.S., Haddad G.G., Karin M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 2008, 453:807-811.
15. Bernhardt W.M., Gottmann U., Doyon F., Buchholz B., Campean V., Schodel J., Reisenbuechler A., Klaus S., Arend M., Flippin L., Willam C., Wiesener M.S., Yard B., Warnecke C., Eckardt K.U. Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model. Proc. Natl. Acad. Sci. U S A 2009, 106:21276-21281.
16. Cummins E.P., Seeballuck F., Keely S.J., Mangan N.E., Callanan J.J., Fallon P.G., Taylor C.T. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 2008, 134:156-165.
17. Zhang Y.L., Radhakrishnan M.L., Lu X., Gross A.W., Tidor B., Lodish H.F. Symmetric signaling by an asymmetric 1 erythropoietin: 2 erythropoietin receptor complex. Mol. Cell. 2009, 33:266-274.
18. Tauchi T., Damen J.E., Toyama K., Feng G.S., Broxmeyer H.E., Krystal G. Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis. Blood 1996, 87:4495-4501.
19. Sinclair A.M., Coxon A., McCaffery I., Kaufman S., Paweletz K., Liu L., Busse L., Swift S., Elliott S., Begley C.G. Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood 2010, 115:4264-4272.
20. Brines M., Cerami A. Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J. Intern. Med. 2008, 264:405-432.
21. Jelkmann W., Bohlius J., Hallek M., Sytkowski A.J. The erythropoietin receptor in normal and cancer tissues. Crit. Rev. Oncol. Hematol. 2008, 67:39-61.
22. Volgger B., Kurz K., Zoschg K., Theurl I., Ciresa-Konig A., Marth C., Weiss G. Importance of erythropoetin receptor expression in tumour tissue for the clinical course of breast cancer. Anticancer Res. 2010, 30:3721-3726.
23. Haq R., Halupa A., Beattie B.K., Mason J.M., Zanke B.W., Barber D.L. Regulation of erythropoietin-induced STAT serine phosphorylation by distinct mitogen-activated protein kinases. J. Biol. Chem. 2002, 277:17359-17366.
24. Carvalho G., Lefaucheur C., Cherbonnier C., Metivier D., Chapel A., Pallardy M., Bourgeade M.F., Charpentier B., Hirsch F., Kroemer G. Chemosensitization by erythropoietin through inhibition of the NF-kappaB rescue pathway. Oncogene 2005, 24:737-745.
25. Nairz M., Schroll A., Moschen A.R., Sonnweber T., Theurl M., Theurl I., Taub N., Jamnig C., Neurauter D., Huber L.A., Tilg H., Moser P.L., Weiss G. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-kappaB-inducible immune pathways. Immunity 2011, 34:61-74.
26. Chen J., Connor K.M., Aderman C.M., Smith L.E. Erythropoietin deficiency decreases vascular stability in mice. J. Clin. Invest. 2008, 118:526-533.
27. Digicaylioglu M., Lipton S.A. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001, 412:641-647.
28. Sulahian R., Cleaver O., Huang L.J. Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia. Blood 2009, 113:5287-5297.
29. Kertesz N., Wu J., Chen T.H., Sucov H.M., Wu H. The role of erythropoietin in regulating angiogenesis. Dev. Biol. 2004, 276:101-110.
30. Choi D., Schroer S.A., Lu S.Y., Wang L., Wu X., Liu Y., Zhang Y., Gaisano H.Y., Wagner K.U., Wu H., Retnakaran R., Woo M. Erythropoietin protects against diabetes through direct effects on pancreatic beta cells. J. Exp. Med. 2010, 207:2831-2842.
31. Parsa C.J., Matsumoto A., Kim J., Riel R.U., Pascal L.S., Walton G.B., Thompson R.B., Petrofski J.A., Annex B.H., Stamler J.S., Koch W.J. A novel protective effect of erythropoietin in the infarcted heart. J. Clin. Invest. 2003, 112:999-1007.
32. Birmingham D.J., Shen X.P., Hartman J.A., Dillon J.J., Hebert L.A. Effect of chronic human recombinant erythropoietin therapy on antibody responses to immunization in chronic hemodialysis patients. Kidney Int. 1996, 50:543-549.
33. Li W., Maeda Y., Yuan R.R., Elkabes S., Cook S., Dowling P. Beneficial effect of erythropoietin on experimental allergic encephalomyelitis. Ann. Neurol. 2004, 56:767-777.
34. Bryl E., Mysliwska J., Debska-Slizien A., Trzonkowski P., Rachon D., Bullo B., Zdrojewski Z., Mysliwski A., Rutkowski B. Recombinant human erythropoietin stimulates production of interleukin 2 by whole blood cell cultures of hemodialysis patients. Artif. Organs 1999, 23:809-816.
35. Agnello D., Bigini P., Villa P., Mennini T., Cerami A., Brines M.L., Ghezzi P. Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res. 2002, 952:128-134.
36. Yuan R., Maeda Y., Li W., Lu W., Cook S., Dowling P. Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE. PLoS One 2008, 3:e1924.
37. Mittelman M., Neumann D., Peled A., Kanter P., Haran-Ghera N. Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proc. Natl. Acad. Sci. U S A 2001, 98:5181-5186.
38. Katz O., Gil L., Lifshitz L., Prutchi-Sagiv S., Gassmann M., Mittelman M., Neumann D. Erythropoietin enhances immune responses in mice. Eur. J. Immunol. 2007, 37:1584-1593.
39. Shurtz-Swirski R., Kristal B., Shasha S.M., Shapiro G., Geron R., Sela S. Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in continuous ambulatory dialysis patients. Nephron 2002, 91:759-761.
40. Lifshitz L., Prutchi-Sagiv S., Avneon M., Gassmann M., Mittelman M., Neumann D. Non-erythroid activities of erythropoietin: functional effects on murine dendritic cells. Mol. Immunol. 2009, 46:713-721.
41. Cuzzocrea S., Mazzon E., di Paola R., Genovese T., Patel N.S., Britti D., de Majo M., Caputi A.P., Thiemermann C. Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse. Arthritis Rheum. 2005, 52:940-950.
42. Hamed S., Egozi D., Kruchevsky D., Teot L., Gilhar A., Ullmann Y. Erythropoietin improves the survival of fat tissue after its transplantation in nude mice. PLoS One 2010, 5:e13986.
43. Kaiser K., Texier A., Ferrandiz J., Buguet A., Meiller A., Latour C., Peyron F., Cespuglio R., Picot S. Recombinant human erythropoietin prevents the death of mice during cerebral malaria. J. Infect. Dis. 2006, 193:987-995.
44. Chang K.H., Tam M., Stevenson M.M. Modulation of the course and outcome of blood-stage malaria by erythropoietin-induced reticulocytosis. J. Infect. Dis. 2004, 189:735-743.
45. Suzuki T., Ueta Y.Y., Inoue N., Xuan X., Saitoh H., Suzuki H. Beneficial effect of erythropoietin administration on murine infection with Trypanosoma congolense. Am. J. Trop. Med. Hyg. 2006, 74:1020-1025.
46. Noyes H.A., Alimohammadian M.H., Agaba M., Brass A., Fuchs H., Gailus-Durner V., Hulme H., Iraqi F., Kemp S., Rathkolb B., Wolf E., de Angelis M.H., Roshandel D., Naessens J. Mechanisms controlling anaemia in Trypanosoma congolense infected mice. PLoS One 2009, 4:e5170.
47. Suliman H.B., Logan-Henfrey L., Majiwa P.A., ole-Moiyoi O., Feldman B.F. Analysis of erythropoietin and erythropoietin receptor genes expression in cattle during acute infection with Trypanosoma congolense. Exp. Hematol. 1999, 27:37-45.
48. Spreer A., Gerber J., Hanssen M., Nau R. No neuroprotective effect of erythropoietin under clinical treatment conditions in a rabbit model of Escherichia coli meningitis. Pediatr. Res. 2007, 62:680-683.
49. Jackson A., Nanton M.R., O'Donnell H., Akue A.D., McSorley S.J. Innate immune activation during Salmonella infection initiates extramedullary erythropoiesis and splenomegaly. J. Immunol. 2010, 185:6198-6204.
50. Napolitano L.M., Fabian T.C., Kelly K.M., Bailey J.A., Block E.F., Langholff W., Enny C., Corwin H.L. Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. J. Trauma 2008, 65:285-297. discussion 297-289.
51. Corwin H.L., Gettinger A., Fabian T.C., May A., Pearl R.G., Heard S., An R., Bowers P.J., Burton P., Klausner M.A., Corwin M.J. Efficacy and safety of epoetin alfa in critically ill patients. N. Engl. J. Med. 2007, 357:965-976.
52. Kumral A., Baskin H., Yesilirmak D.C., Ergur B.U., Aykan S., Genc S., Genc K., Yilmaz O., Tugyan K., Giray O., Duman N., Ozkan H. Erythropoietin attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain. Neonatology 2007, 92:269-278.
53. Mitra A., Bansal S., Wang W., Falk S., Zolty E., Schrier R.W. Erythropoietin ameliorates renal dysfunction during endotoxaemia. Nephrol. Dial. Transplant. 2007, 22:2349-2353.
54. Wagner M., Alam A., Zimmermann J., Rauh K., Koljaja-Batzner A., Raff U., Wanner C., Schramm L. Endogenous erythropoietin and the association with inflammation and mortality in diabetic chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2011, 6:1573-1579.
55. Brines M., Grasso G., Fiordaliso F., Sfacteria A., Ghezzi P., Fratelli M., Latini R., Xie Q.W., Smart J., Su-Rick C.J., Pobre E., Diaz D., Gomez D., Hand C., Coleman T., Cerami A. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc. Natl. Acad. Sci. U S A 2004, 101:14907-14912.
56. Macdougall I.C., Rossert J., Casadevall N., Stead R.B., Duliege A.M., Froissart M., Eckardt K.U. A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. N. Engl. J. Med. 2009, 361:1848-1855.
57. Wrighton N.C., Farrell F.X., Chang R., Kashyap A.K., Barbone F.P., Mulcahy L.S., Johnson D.L., Barrett R.W., Jolliffe L.K., Dower W.J. Small peptides as potent mimetics of the protein hormone erythropoietin. Science 1996, 273:458-464.
58. Brines M., Patel N.S., Villa P., Brines C., Mennini T., De Paola M., Erbayraktar Z., Erbayraktar S., Sepodes B., Thiemermann C., Ghezzi P., Yamin M., Hand C.C., Xie Q.W., Coleman T., Cerami A. Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc. Natl. Acad. Sci. U S A 2008, 105:10925-10930.
59. Polgarova K., Luthje P., Cerami A., Brauner A. The erythropoietin analogue ARA290 modulates the innate immune response and reduces Escherichia coli invasion into urothelial cells. FEMS Immunol. Med. Microbiol. 2011, 62:190-196.
60. Erbayraktar Z., Erbayraktar S., Yilmaz O., Cerami A., Coleman T., Brines M. Nonerythropoietic tissue protective compounds are highly effective facilitators of wound healing. Mol. Med. 2009, 15:235-241.
61. Solomon S.D., Uno H., Lewis E.F., Eckardt K.U., Lin J., Burdmann E.A., de Zeeuw D., Ivanovich P., Levey A.S., Parfrey P., Remuzzi G., Singh A.K., Toto R., Huang F., Rossert J., McMurray J.J., Pfeffer M.A. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N. Engl. J. Med. 2010, 363:1146-1155.
62. Broxmeyer H.E. Erythropoietin surprises: an immune saga. Immunity 2011, 34:6-7.
63. Karin M., Greten F.R. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 2005, 5:749-759.
64. Sadikot R.T., Zeng H., Joo M., Everhart M.B., Sherrill T.P., Li B., Cheng D.S., Yull F.E., Christman J.W., Blackwell T.S. Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa. J. Immunol. 2006, 176:4923-4930.
65. Gjertsson I., Hultgren O.H., Collins L.V., Pettersson S., Tarkowski A. Impact of transcription factors AP-1 and NF-kappaB on the outcome of experimental Staphylococcus aureus arthritis and sepsis. Microbes Infect. 2001, 3:527-534.
66. Sha W.C., Liou H.C., Tuomanen E.I., Baltimore D. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell 1995, 80:321-330.
67. Jantsch J., Wiese M., Schodel J., Castiglione K., Glasner J., Kolbe S., Mole D., Schleicher U., Eckardt K.U., Hensel M., Lang R., Bogdan C., Schnare M., Willam C. Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1{alpha} (HIF1A) and result in differential HIF1A-dependent gene expression. J. Leukoc. Biol. 2011, 90:551-562.
68. Walmsley S.R., Print C., Farahi N., Peyssonnaux C., Johnson R.S., Cramer T., Sobolewski A., Condliffe A.M., Cowburn A.S., Johnson N., Chilvers E.R. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J. Exp. Med. 2005, 201:105-115.
69. Peyssonnaux C., Nizet V., Johnson R.S. Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle 2008, 7:28-32.
70. Weiss G., Houston T., Kastner S., Johrer K., Grunewald K., Brock J.H. Regulation of cellular iron metabolism by erythropoietin: activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells. Blood 1997, 89:680-687.
71. Dlaska M., Weiss G. Central role of transcription factor NF-IL6 for cytokine and iron-mediated regulation of murine inducible nitric oxide synthase expression. J. Immunol. 1999, 162:6171-6177.
72. Oexle H., Kaser A., Most J., Bellmann-Weiler R., Werner E.R., Werner-Felmayer G., Weiss G. Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells. J. Leukoc. Biol. 2003, 74:287-294.
73. Recalcati S., Pometta R., Levi S., Conte D., Cairo G. Response of monocyte iron regulatory protein activity to inflammation: abnormal behavior in genetic hemochromatosis. Blood 1998, 91:2565-2572.
74. Nairz M., Schroll A., Sonnweber T., Weiss G. The struggle for iron - a metal at the host-pathogen interface. Cell. Microbiol. 2010, 12:1691-1702.
75. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003, 102:783-788.
76. Hentze M.W., Muckenthaler M.U., Galy B., Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell 2010, 142:24-38.
77. Theurl I., Theurl M., Seifert M., Mair S., Nairz M., Rumpold H., Zoller H., Bellmann-Weiler R., Niederegger H., Talasz H., Weiss G. Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 2008, 111:2392-2399.
78. Robach P., Recalcati S., Girelli D., Gelfi C., Aachmann-Andersen N.J., Thomsen J.J., Norgaard A.M., Alberghini A., Campostrini N., Castagna A., Vigano A., Santambrogio P., Kempf T., Wollert K.C., Moutereau S., Lundby C., Cairo G. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. Blood 2009, 113:6707-6715.
79. Weiss G., Werner-Felmayer G., Werner E.R., Grunewald K., Wachter H., Hentze M.W. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J. Exp. Med. 1994, 180:969-976.
80. De Domenico I., Zhang T.Y., Koening C.L., Branch R.W., London N., Lo E., Daynes R.A., Kushner J.P., Li D., Ward D.M., Kaplan J. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J. Clin. Invest. 2010, 120:2395-2405.
81. Pagani A., Nai A., Corna G., Bosurgi L., Rovere-Querini P., Camaschella C., Silvestri L. Low hepcidin accounts for the proinflammatory status associated with iron deficiency. Blood 2011, 118:736-746.
82. Portugal S., Carret C., Recker M., Armitage A.E., Goncalves L.A., Epiphanio S., Sullivan D., Roy C., Newbold C.I., Drakesmith H., Mota M.M. Host-mediated regulation of superinfection in malaria. Nat. Med. 2011, 17:732-737.