Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile

Abstract Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Federica Gaiani, Bianca Maria Rotoli, Francesca Ferrari, Amelia Barilli, Rossana Visigalli, Maria Clotilde Carra, Gian Luigi de’Angelis, Nicola de’Angelis, Valeria Dall’Asta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8636936dc86841a397cc30500d3d886e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8636936dc86841a397cc30500d3d886e
record_format	dspace
spelling	oai:doaj.org-article:8636936dc86841a397cc30500d3d886e2021-12-02T16:26:37ZMonocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile10.1038/s41598-020-68993-12045-2322https://doaj.org/article/8636936dc86841a397cc30500d3d886e2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68993-1https://doaj.org/toc/2045-2322Abstract Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes’ cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.Federica GaianiBianca Maria RotoliFrancesca FerrariAmelia BarilliRossana VisigalliMaria Clotilde CarraGian Luigi de’AngelisNicola de’AngelisValeria Dall’AstaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Federica Gaiani Bianca Maria Rotoli Francesca Ferrari Amelia Barilli Rossana Visigalli Maria Clotilde Carra Gian Luigi de’Angelis Nicola de’Angelis Valeria Dall’Asta Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
description	Abstract Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes’ cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.
format	article
author	Federica Gaiani Bianca Maria Rotoli Francesca Ferrari Amelia Barilli Rossana Visigalli Maria Clotilde Carra Gian Luigi de’Angelis Nicola de’Angelis Valeria Dall’Asta
author_facet	Federica Gaiani Bianca Maria Rotoli Francesca Ferrari Amelia Barilli Rossana Visigalli Maria Clotilde Carra Gian Luigi de’Angelis Nicola de’Angelis Valeria Dall’Asta
author_sort	Federica Gaiani
title	Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
title_short	Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
title_full	Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
title_fullStr	Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
title_full_unstemmed	Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
title_sort	monocytes from infliximab-resistant patients with crohn’s disease exhibit a disordered cytokine profile
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8636936dc86841a397cc30500d3d886e
work_keys_str_mv	AT federicagaiani monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT biancamariarotoli monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT francescaferrari monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT ameliabarilli monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT rossanavisigalli monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT mariaclotildecarra monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT gianluigideangelis monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT nicoladeangelis monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile AT valeriadallasta monocytesfrominfliximabresistantpatientswithcrohnsdiseaseexhibitadisorderedcytokineprofile
_version_	1718384001532559360

Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile

Ejemplares similares