Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells

An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several...

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Main Authors: Susann A. Dorosz, Aurélien Ginolhac, Thilo Kähne, Michael Naumann, Thomas Sauter, Alexandre Salsmann, Jean-Luc Bueb
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/737310
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author Susann A. Dorosz
Aurélien Ginolhac
Thilo Kähne
Michael Naumann
Thomas Sauter
Alexandre Salsmann
Jean-Luc Bueb
author_facet Susann A. Dorosz
Aurélien Ginolhac
Thilo Kähne
Michael Naumann
Thomas Sauter
Alexandre Salsmann
Jean-Luc Bueb
author_sort Susann A. Dorosz
collection DOAJ
description An underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.
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spelling doaj-art-3c606dc4af244fb0a70e8105fbc772f62025-08-20T02:39:11ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/737310737310Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial CellsSusann A. Dorosz0Aurélien Ginolhac1Thilo Kähne2Michael Naumann3Thomas Sauter4Alexandre Salsmann5Jean-Luc Bueb6Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, LuxembourgLife Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, LuxembourgInstitute for Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyInstitute for Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyLife Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, LuxembourgLife Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, LuxembourgLife Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, LuxembourgAn underlying endothelial dysfunction plays a fundamental role in the pathogenesis of cardiovascular events and is the central feature of atherosclerosis. The protein-based communication between leukocytes and inflamed endothelial cells leading to diapedesis has been largely investigated and several key players such as IL6, TNFα, or the damage associated molecular pattern molecule (DAMP) calprotectin are now well identified. However, regarding cytokine IL27, the controversial current knowledge about its inflammatory role and the involved regulatory elements requires clarification. Therefore, we examined the inflammatory impact of IL27 on primary endothelial cells and the potentially modulatory effect of calprotectin on both transcriptome and proteome levels. A qPCR-based screening demonstrated high IL27-mediated gene expression of IL7, IL15, CXCL10, and CXCL11. Calprotectin time-dependent downregulatory effects were observed on IL27-induced IL15 and CXCL10 gene expression. A mass spectrometry-based approach of IL27 ± calprotectin cell stimulation enlightened a calprotectin modulatory role in the expression of 28 proteins, mostly involved in the mechanism of leukocyte transmigration. Furthermore, we showed evidence for STAT1 involvement in this process. Our findings provide new evidence about the IL27-dependent proinflammatory signaling which may be under the control of calprotectin and highlight the need for further investigations on molecules which might have antiatherosclerotic functions.http://dx.doi.org/10.1155/2015/737310
spellingShingle Susann A. Dorosz
Aurélien Ginolhac
Thilo Kähne
Michael Naumann
Thomas Sauter
Alexandre Salsmann
Jean-Luc Bueb
Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
Mediators of Inflammation
title Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
title_full Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
title_fullStr Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
title_full_unstemmed Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
title_short Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells
title_sort role of calprotectin as a modulator of the il27 mediated proinflammatory effect on endothelial cells
url http://dx.doi.org/10.1155/2015/737310
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