title: Role of Calprotectin as a Modulator of the IL27-Mediated Proinflammatory Effect on Endothelial Cells.
abstract: 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.
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.
authors.forename: Susann A
authors.identifier: 0000-0003-2913-1365
authors.initials: SA
authors.lastname: Dorosz
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Ginolhac
authors.affiliation: Institute for Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Kähne
authors.affiliation: Institute for Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany.
authors.forename: Michael
authors.identifier: 0000-0002-8060-2313
authors.initials: M
authors.lastname: Naumann
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sauter
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Salsmann
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, 162a Avenue de la Faïencerie, 1511 Luxembourg City, Luxembourg.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bueb
mesh_terms: D050197:Atherosclerosis / Q000209:etiology* / Q000517:prevention & control; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics; D064094:Interleukin-27 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000235:genetics; D039841:Leukocyte L1 Antigen Complex / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C569274:IL15 protein, human; D019409:Interleukin-15; D064094:Interleukin-27; D015851:Interleukin-7; D039841:Leukocyte L1 Antigen Complex; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human