Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis

Abstract Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (...

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Autores principales:	Manfred Nairz, David Haschka, Stefanie Dichtl, Thomas Sonnweber, Andrea Schroll, Malte Aßhoff, John E. Mindur, Patrizia L. Moser, Dominik Wolf, Filip K. Swirski, Igor Theurl, Anthony Cerami, Michael Brines, Günter Weiss
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d221a86842e477ebdfddad36073f220
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spelling	oai:doaj.org-article:3d221a86842e477ebdfddad36073f2202021-12-02T15:06:15ZCibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis10.1038/s41598-017-13046-32045-2322https://doaj.org/article/3d221a86842e477ebdfddad36073f2202017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13046-3https://doaj.org/toc/2045-2322Abstract Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide. We found that both cibinetide and EPO ameliorated the clinical course of experimental colitis in mice, resulting in improved weight gain and survival. Correspondingly, DSS-exposed mice treated with cibinetide or EPO displayed preserved tissue integrity due to reduced infiltration of myeloid cells and diminished production of pro-inflammatory disease mediators including cytokines, chemokines and nitric oxide synthase-2. Experiments using LPS-activated primary macrophages revealed that the anti-inflammatory effects of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF-κB subunit p65 activity. Cibinetide activation of the IRR exerts potent anti-inflammatory effects, especially within the myeloid population, reduces disease activity and mortality in mice. Cibinetide thus holds promise as novel disease-modifying therapeutic of inflammatory bowel disease.Manfred NairzDavid HaschkaStefanie DichtlThomas SonnweberAndrea SchrollMalte AßhoffJohn E. MindurPatrizia L. MoserDominik WolfFilip K. SwirskiIgor TheurlAnthony CeramiMichael BrinesGünter WeissNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manfred Nairz David Haschka Stefanie Dichtl Thomas Sonnweber Andrea Schroll Malte Aßhoff John E. Mindur Patrizia L. Moser Dominik Wolf Filip K. Swirski Igor Theurl Anthony Cerami Michael Brines Günter Weiss Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
description	Abstract Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide. We found that both cibinetide and EPO ameliorated the clinical course of experimental colitis in mice, resulting in improved weight gain and survival. Correspondingly, DSS-exposed mice treated with cibinetide or EPO displayed preserved tissue integrity due to reduced infiltration of myeloid cells and diminished production of pro-inflammatory disease mediators including cytokines, chemokines and nitric oxide synthase-2. Experiments using LPS-activated primary macrophages revealed that the anti-inflammatory effects of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF-κB subunit p65 activity. Cibinetide activation of the IRR exerts potent anti-inflammatory effects, especially within the myeloid population, reduces disease activity and mortality in mice. Cibinetide thus holds promise as novel disease-modifying therapeutic of inflammatory bowel disease.
format	article
author	Manfred Nairz David Haschka Stefanie Dichtl Thomas Sonnweber Andrea Schroll Malte Aßhoff John E. Mindur Patrizia L. Moser Dominik Wolf Filip K. Swirski Igor Theurl Anthony Cerami Michael Brines Günter Weiss
author_facet	Manfred Nairz David Haschka Stefanie Dichtl Thomas Sonnweber Andrea Schroll Malte Aßhoff John E. Mindur Patrizia L. Moser Dominik Wolf Filip K. Swirski Igor Theurl Anthony Cerami Michael Brines Günter Weiss
author_sort	Manfred Nairz
title	Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
title_short	Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
title_full	Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
title_fullStr	Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
title_full_unstemmed	Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
title_sort	cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3d221a86842e477ebdfddad36073f220
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Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis

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