Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells

The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we foc...

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Main Authors: Andreas Schmid, Ann-Kathrin Vlacil, Jutta Schuett, Thomas Karrasch, Bernhard Schieffer, Andreas Schäffler, Karsten Grote
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/8/2146
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author Andreas Schmid
Ann-Kathrin Vlacil
Jutta Schuett
Thomas Karrasch
Bernhard Schieffer
Andreas Schäffler
Karsten Grote
author_facet Andreas Schmid
Ann-Kathrin Vlacil
Jutta Schuett
Thomas Karrasch
Bernhard Schieffer
Andreas Schäffler
Karsten Grote
author_sort Andreas Schmid
collection DOAJ
description The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin <i>(Il)-6</i> and the tumor necrosis factor <i>(Tnf)-α</i>, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules <i>Vcam-1</i> and <i>Icam-1</i>. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia.
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spelling doaj.art-dc32a4e76f8446fd97f0bc1749c74fc82023-11-22T07:12:22ZengMDPI AGCells2073-44092021-08-01108214610.3390/cells10082146Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial CellsAndreas Schmid0Ann-Kathrin Vlacil1Jutta Schuett2Thomas Karrasch3Bernhard Schieffer4Andreas Schäffler5Karsten Grote6Department of Internal Medicine III, University of Giessen, 35390 Giessen, GermanyDepartment of Cardiology and Angiology, Philipps-University Marburg, 35037 Marburg, GermanyDepartment of Cardiology and Angiology, Philipps-University Marburg, 35037 Marburg, GermanyDepartment of Internal Medicine III, University of Giessen, 35390 Giessen, GermanyDepartment of Cardiology and Angiology, Philipps-University Marburg, 35037 Marburg, GermanyDepartment of Internal Medicine III, University of Giessen, 35390 Giessen, GermanyDepartment of Cardiology and Angiology, Philipps-University Marburg, 35037 Marburg, GermanyThe C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin <i>(Il)-6</i> and the tumor necrosis factor <i>(Tnf)-α</i>, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules <i>Vcam-1</i> and <i>Icam-1</i>. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia.https://www.mdpi.com/2073-4409/10/8/2146endothelial cellsinfectioninflammationendotoxinCTRP3adipocytes
spellingShingle Andreas Schmid
Ann-Kathrin Vlacil
Jutta Schuett
Thomas Karrasch
Bernhard Schieffer
Andreas Schäffler
Karsten Grote
Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
Cells
endothelial cells
infection
inflammation
endotoxin
CTRP3
adipocytes
title Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
title_full Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
title_fullStr Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
title_full_unstemmed Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
title_short Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells
title_sort anti inflammatory effects of c1q tumor necrosis factor related protein 3 ctrp3 in endothelial cells
topic endothelial cells
infection
inflammation
endotoxin
CTRP3
adipocytes
url https://www.mdpi.com/2073-4409/10/8/2146
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