1. CD40L/CD40 Regulates Adipokines and Cytokines by H3K4me3 Modification in Epicardial Adipocytes.
- Author
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Yuan M, Wu B, Zhang L, Wang H, and Yang Y
- Subjects
- Adipocytes metabolism, Adipokines genetics, Aged, CD40 Antigens genetics, CD40 Antigens metabolism, Case-Control Studies, Cells, Cultured, Chemokine CCL2 genetics, Chemokine CCL2 metabolism, Cytokines genetics, Female, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Humans, Interleukin-6 genetics, Interleukin-6 metabolism, Leptin genetics, Leptin metabolism, Male, Methylation, Middle Aged, Myeloid-Lymphoid Leukemia Protein genetics, Myeloid-Lymphoid Leukemia Protein metabolism, Pericardium metabolism, Plasminogen Activator Inhibitor 1 genetics, Plasminogen Activator Inhibitor 1 metabolism, Promoter Regions, Genetic, Protein Processing, Post-Translational, Adipocytes drug effects, Adipokines metabolism, CD40 Antigens agonists, CD40 Ligand pharmacology, Coronary Artery Disease metabolism, Cytokines metabolism, Histones metabolism, Pericardium drug effects
- Abstract
Abstract: Epicardial adipose tissue (EAT) dysfunction mediates chronic inflammation by regulating inflammation-related adipokines and cytokines, and it further promotes coronary artery disease (CAD) development. CD40L/CD40 is involved in multiple inflammatory pathways that contribute to various pathophysiological processes. However, the function of CD40L/CD40 in the expression and production of adipokines and cytokines in epicardial adipocytes remains unclear. The purpose of the present study was to explore the role and underlying mechanisms of CD40L/CD40 in adipokine and cytokine expression and production. We isolated adipocytes from EAT tissues of CAD and non-CAD patients. We noticed that CD40 was dramatically increased in EAT tissues of CAD patients. Loss-of-function and gain-of-function studies were performed. The results showed that CD40 silencing reduced recombinant CD40 ligand (rCD40L)-induced upregulation of plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 messenger RNA levels and secretion. Overexpression of CD40 displayed the opposite results. In addition, rCD40L triggered mixed lineage leukemia protein-1 (MLL1) expression both in messenger RNA and protein levels. CD40 depletion apparently blocked MLL1 expression, whereas gain of function of CD40 resulted in augmentation of MLL1 levels. Interestingly, chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis revealed that CD40 elimination dampened histone H3 lysine 4 trimethylation enrichment at plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 promoter regions in the presence of rCD40L. The reverse pattern was observed upon ectopic expression of CD40. Most important, MLL1 silencing effectively reversed the promotive effects of CD40 on adipokine and cytokine secretion. Taken together, our findings suggest that CD40L/CD40 regulates adipokine and cytokine expression by H3 lysine 4 trimethylation modification in adipocytes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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