Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-κB-inducible immune pathways

Manfred Nairz; Andrea Schroll; Alexander R Moschen; Thomas Sonnweber; Milan Theurl; Igor Theurl; Nicole Taub; Christina Jamnig; Daniela Neurauter; Lukas A Huber; Herbert Tilg; Patrizia L Moser; Günter Weiss

doi:10.1016/j.immuni.2011.01.002

Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-κB-inducible immune pathways

Immunity. 2011 Jan 28;34(1):61-74. doi: 10.1016/j.immuni.2011.01.002. Epub 2011 Jan 20.

Authors

Manfred Nairz¹, Andrea Schroll, Alexander R Moschen, Thomas Sonnweber, Milan Theurl, Igor Theurl, Nicole Taub, Christina Jamnig, Daniela Neurauter, Lukas A Huber, Herbert Tilg, Patrizia L Moser, Günter Weiss

Affiliation

¹ Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, 6020 Innsbruck, Austria.

Abstract

Erythropoietin (EPO) is the principal cytokine regulating erythropoiesis through its receptor, EPOR. Interestingly, EPORs are also found on immune cells with incompletely understood functions. Here, we show that EPO inhibits the induction of proinflammatory genes including tumor necrosis factor (TNF)-α and inducible nitric oxide (NO) synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor (NF)-κB p65 activation by EPO. Accordingly, in systemic Salmonella infection, treatment of mice with EPO results in reduced survival and impaired pathogen clearance because of diminished formation of anti-microbial effector molecules such as TNF-α and NO. However, neutralization of endogenous EPO or genetic ablation of Epor promotes Salmonella elimination. In contrast, in chemically induced colitis, EPO-EPOR interaction decreases the production of NF-κB-inducible immune mediators, thus limiting tissue damage and ameliorating disease severity. These immune-modulatory effects of EPO may be of therapeutic relevance in infectious and inflammatory diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Colitis / chemically induced
Colitis / drug therapy
Colitis / immunology*
Dextran Sulfate / administration & dosage
Erythropoietin / administration & dosage*
Humans
Inflammation Mediators / metabolism
Macrophages, Peritoneal / drug effects*
Macrophages, Peritoneal / immunology
Macrophages, Peritoneal / metabolism
Macrophages, Peritoneal / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B / metabolism*
Nitric Oxide / immunology
Nitric Oxide / metabolism
Receptors, Erythropoietin / genetics
Receptors, Erythropoietin / metabolism*
Salmonella / immunology*
Salmonella / pathogenicity
Salmonella Infections / drug therapy
Salmonella Infections / immunology*
Signal Transduction / drug effects
Signal Transduction / genetics
Signal Transduction / immunology
Trinitrobenzenesulfonic Acid / administration & dosage
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology
Tumor Necrosis Factor-alpha / metabolism

Substances

Inflammation Mediators
NF-kappa B
Receptors, Erythropoietin
Tumor Necrosis Factor-alpha
Erythropoietin
Nitric Oxide
Trinitrobenzenesulfonic Acid
Dextran Sulfate