高糖对THP-1细胞及平滑肌细胞肿瘤坏死因子相关凋亡诱导配体受体4表达的影响

High glucose up-regulates TRAIL-R4 expression in THP-1 cells and smooth muscle cells

目的:探讨高糖对单核/巨噬细胞系THP-1细胞及人主动脉平滑肌细胞肿瘤坏死因子相关凋亡诱导配体受体4(TRAIL-R4)表达的影响。方法:用PMA孵育THP-1细胞,诱导其分化成为巨噬细胞。流式细胞仪检测成功诱导的巨噬细胞粘附分子CD11b及CD11c。采用不同糖浓度干预THP-1细胞,用Western blotting技术检测TRAIL-R4的表达。用25mmol/L高糖培养液在不同时点孵育人主动脉平滑肌细胞,观察TRAIL-R4蛋白表达的变化。用PKC激动剂干预THP-1细胞后,用Western blotting技术检测TRAIL-R4的表达。结果:佛波酯(PMA)孵育THP-1细胞48h可诱导其分化成为巨噬细胞。20mmol/L高糖明显上调人THP-1细胞TRAIL-R4的表达。高糖对人主动脉平滑肌细胞TRAIL-R4表达上调的影响随着刺激时间的增加而增加。PKC激活后THP-1细胞TRAIL-R4的表达明显上调。结论:高糖上调TRAIL-R4蛋白表达,TRAIL-R4通过抑制巨噬细胞及平滑肌细胞的凋亡促进动脉粥样硬化。

AIM：To evaluate the expression of TNF - related apoptosis inducing ligand receptor 4 （ TRAIL -R4） of THP- 1 cells and human aorta Smooth muscle cells under high glucose intervention. METHODS： Monocytic cell line THP - 1 was incubated with PMA to induce to mature macrophage, Adhesion molecules CDllb and CDllc were assessed by FACS. TRAIL - R4 levels in THP - 1 cells treated with different glucose concentrations were determined by Western blotting. The changes of TRAIL - R4 protein expressions were observed at different time points in human aorta smooth muscle cells. Western blotting was employed to evaluate TRAIL - R4 levels after the intervention of PKC activator. RESULTS： Incubation with 160 nmol/L PMA induced mature macrophages. TRAIL- R4 expression was up-regulated after incubation with 20 mmol/L glucose in macrophages. TRAIL - R4 was elevated in a time course manner under high glucose level in human aorta smooth muscle cells. Moreover, activation of PKC induced TRAIL - R4 expressions. CON- CLUSION： Up-regulated TRAIL- R4 protein levels induced by high glucose levels might inhibit apoptosis of monocytes and smooth muscle cells and contribute to the progression of atherosclerosis.