blockade of t cell contact-activation of human monocytes by high-density lipoproteins reveals a new pattern of cytokine and inflammatory genest细胞的封锁contact-activation高密度脂蛋白揭示人类单核细胞的细胞因子和炎症基因的新模式.pdf

Blockade of T Cell Contact-Activation of Human Monocytes by High-Density Lipoproteins Reveals a New Pattern of Cytokine and Inflammatory Genes 1 ´ 2 2 3 1 Lyssia Gruaz , Celine Delucinge-Vivier , Patrick Descombes , Jean-Michel Dayer , Danielle Burger * 1 Division of Immunology and Allergy, Inflammation and Allergy Research Group, Hans Wilsdorf Laboratory, Department of Internal Medicine and Faculty of Medicine, University of Geneva, Geneva, Switzerland, 2 Genomics Platform, National Center of Competence in Research ‘Frontiers in Genetics’, University of Geneva, Geneva, Switzerland, 3 Faculty of Medicine, University of Geneva, Geneva, Switzerland Abstract Background: Cellular contact with stimulated T cells is a potent inducer of cytokine production in human monocytes and is likely to play a substantial part in chronic/sterile inflammatory diseases. High-density lipoproteins (HDL) specifically inhibit the production of pro-inflammatory cytokines induced by T cell contact. Methodology/Principal Findings: To further elucidate the pro-inflammatory functions of cellular contact with stimulated T cells and its inhibition by HDL, we carried out multiplex and microarray analyses. Multiplex analysis of monocyte supernatant revealed that 12 out of 27 cytokines were induced upon contact with stimulated T cells, which cytokines included IL-1Ra, G-CSF, GM-CSF, IFNc, CCL2, CCL5, TNF, IL-1b, IL-6, IL-8, CCL3, and CCL4, but only the latter six were inhibited by HDL. Microarray analysis showed that 437 out of 54,675 probe sets were enhanced in monocytes activated by contact with stimulated T cells, 164 probe sets (i.e., 38%) being inhibited by HDL. These results were validated by qPCR. Interestin