RRC ID 11860
Author Nairz M, Schroll A, Moschen AR, Sonnweber T, Theurl M, Theurl I, Taub N, Jamnig C, Neurauter D, Huber LA, Tilg H, Moser PL, Weiss G.
Title Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-κB-inducible immune pathways.
Journal Immunity
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.
Volume 34(1)
Pages 61-74
Published 2011-1-28
DOI 10.1016/j.immuni.2011.01.002
PII S1074-7613(11)00003-3
PMID 21256055
PMC PMC3032045
MeSH 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
IF 19.734
Times Cited 80
Mice EpoR(-/-) ::HG1-EpoR mouse