Chávez-Sánchez Luis, Garza-Reyes Montserrat Guadalupe, Espinosa-Luna José Esteban, Chávez-Rueda Karina, Legorreta-Haquet María Victoria, Blanco-Favela Francisco
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico.
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico; Departamento de Inmunología, ENCB, IPN, México D.F., Mexico.
Hum Immunol. 2014 Apr;75(4):322-9. doi: 10.1016/j.humimm.2014.01.012. Epub 2014 Jan 30.
Toll-like receptor (TLR)2, TLR4 and CD36 are central in inflammation and the development of atherosclerosis. Oxidized low-density lipoprotein (oxLDL) plays a critical role in this disease through its involvement in the formation of foam cells and the activation of leukocytes. The aim of this research was to analyze the role of TLR2, TLR4 and CD36 in foam cell differentiation and macrophage activation.
Human macrophages were incubated with monoclonal antibodies specific for TLR2, TLR4 and CD36 prior to stimulation with oxLDL. Subsequently, we analyzed foam cell formation, cytokine secretion, histocompatibility complex (MHC) class II molecules and CD86 expression and T cell proliferation.
The stimulation of macrophages with oxLDL induced foam cell formation, cytokine secretion, HLA-DR and CD86 expression and T cell proliferation. The blockage of TLR2, TLR4 and CD36 reduced the secretion of IL-1β, IL-6 and IL-8, the expression of HLA-DR and CD86, T cell proliferation and foam cell formation. However, the blockage of TLR2 did not affect the formation of foam cells.
Our study demonstrates that TLR2, TLR4 and CD36 participate in the immune response to oxLDL by inducing an increase in pro-inflammatory cytokines, the expression HLA-DR and CD86 and the proliferation of T cells. However, TLR2 does not participate in the formation of foam cells, while TLR4 and CD36 play a relevant role in this process. These findings suggest that the activation of these receptors by oxLDL contributes to the pathogenesis of atherosclerosis.
Toll样受体（TLR）2、TLR4和CD36在炎症和动脉粥样硬化的发展中起核心作用。氧化型低密度脂蛋白（oxLDL）通过参与泡沫细胞的形成和白细胞的激活在该疾病中起关键作用。本研究的目的是分析TLR2、TLR4和CD36在泡沫细胞分化和巨噬细胞激活中的作用。
在用oxLDL刺激之前，将人巨噬细胞与针对TLR2、TLR4和CD36的单克隆抗体孵育。随后，我们分析了泡沫细胞的形成、细胞因子分泌、组织相容性复合体（MHC）II类分子和CD86表达以及T细胞增殖。
用oxLDL刺激巨噬细胞可诱导泡沫细胞形成、细胞因子分泌、HLA-DR和CD86表达以及T细胞增殖。阻断TLR2、TLR4和CD36可减少IL-1β、IL-6和IL-8的分泌、HLA-DR和CD86的表达、T细胞增殖以及泡沫细胞形成。然而，阻断TLR2并不影响泡沫细胞的形成。
我们的研究表明，TLR2、TLR4和CD36通过诱导促炎细胞因子增加、HLA-DR和CD86表达以及T细胞增殖参与对oxLDL的免疫反应。然而，TLR2不参与泡沫细胞的形成，而TLR4和CD36在此过程中起相关作用。这些发现表明，oxLDL对这些受体的激活有助于动脉粥样硬化的发病机制。
