1. Anti-Inflammatory Effects of C1q/Tumor Necrosis Factor-Related Protein 3 (CTRP3) in Endothelial Cells.
- Author
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Schmid A, Vlacil AK, Schuett J, Karrasch T, Schieffer B, Schäffler A, and Grote K
- Subjects
- Adipokines genetics, Adipokines metabolism, Adipose Tissue metabolism, Animals, Cell Adhesion drug effects, Cell Adhesion genetics, Cell Adhesion immunology, Cell Adhesion Molecules genetics, Cell Adhesion Molecules immunology, Cell Adhesion Molecules metabolism, Cell Line, Cytokines genetics, Cytokines immunology, Cytokines metabolism, Endothelial Cells drug effects, Endothelial Cells metabolism, Gene Expression Regulation drug effects, Gene Expression Regulation immunology, Humans, Inflammation genetics, Inflammation metabolism, Lipopolysaccharides pharmacology, Male, Mice, Inbred C57BL, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 immunology, Toll-Like Receptor 4 metabolism, Mice, Adipokines immunology, Adipose Tissue immunology, Endothelial Cells immunology, Gene Expression Profiling, Inflammation immunology
- Abstract
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 (Il)-6 and the tumor necrosis factor (Tnf)-α , and suppressed the LPS-dependent expression of the major endothelial adhesion molecules Vcam-1 and Icam-1 . 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.
- Published
- 2021
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