Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response
Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response
复制标题
DOI：
10.4049/jimmunol.179.5.3242
复制
发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Cenarro, Ana
中科院分区：
文献类型：
--
作者：
Martin-Fuentes, Paula;Civeira, Fernando;Cenarro, Ana
动脉粥样硬化是一种炎症性疾病，其中氧化低密度脂蛋白（oxLDL）起着重要作用。清道夫受体（SR）CD 36、SR-A和LOX-1摄取超过90%的oxLDL，导致泡沫细胞形成和炎性细胞因子的分泌。为了研究巨噬细胞SR基因表达的个体间差异是否可以决定对oxLDL反应的炎症变异性，我们定量了从18名志愿受试者中分离的巨噬细胞中SR和炎症分子的基因和蛋白表达，并与oxLDL孵育1，3，6和18小时。在孵育1小时时，研究的SR的单个基因表达谱高度可变，显示出宽的倍数变化范围：CD 36：-3.57-4.22，SR-A：-5.0-4.43，LOX-P -1.56-75.32。我们根据受试者的SR基因表达是否高于或低于中位数将受试者分为高反应者和低反应者，显示出不同的炎症反应模式。CD 36、LOX-1基因表达与IL-10呈正相关，SR-A与IL-8呈负相关，与PPAR γ、NF-κ BIA呈正相关。这些结果在第一次采样后3个月在相同受试者中得到证实。oxLDL孵育18 h后，CD 36与SR-A蛋白水平呈负相关（R =-0.926，p = 0.024）。这些数据表明SR的类型可以决定巨噬细胞的活化：与CD 36和LOX-1相关时比与SR-A相关时更促炎。
Atherosclerosis is an inflammatory disease in which oxidized low-density lipoprotein (oxLDL) plays important roles. Scavenger receptors (SR) CD36, SR-A, and LOX-1 uptake over 90% of the oxLDL leading to foam cell formation and secretion of inflammatory cytokines. To investigate whether the interindividuall differences in macrophage SR gene expression could determine the inflammatory variability in response to oxLDL, we quantified the gene and protein expression of SR and inflammatory molecules from macrophages isolated from 18 volunteer subjects and incubated with oxLDL for 1, 3, 6, and 18 h. The individual gene expression profile of the studied SR at 1 h of incubation was highly variable, showing a wide fold-change range: CD36: -3.57-4.22, SR-A: -5.0-4.43, and LOX-P -1.56-75.32. We identified subjects as high and low responders depending on whether their SR gene expression Was above or below the median, showing a different inflammation response pattern. CD36 and LOX-] gene expression correlated positively withIL-10; SR-A correlated negatively withIL-8 and positively withPPAR gamma andNF-KBIA. These results were confirmed in the same subjects 3 mo after the first sampling. Furthermore, a negative correlation existed between CD36 and SR-A at protein level after 18 h of oxLDL incubation (R = - 0.926, p = 0.024). These data would suggest that the type of SR could determine the macrophage activation: more proinflammatory when associated to CD36 and LOX-1 than when associated with SR-A.