罗格列酮对RAW 264.7细胞源性泡沫细胞炎症反应及SOCS1和SOCS3表达的影响

 目的:观察过氧化物酶体增殖物激活受体γ（PPARγ）配体罗格列酮是否能够调节泡沫细胞促炎/抗炎反应以及细胞因子信号抑制物1（SOCS1）和细胞因子信号抑制物3（SOCS3）的表达。方法:采用ELISA法测定泡沫细胞培养液中肿瘤坏死因子α (TNF-α)、白细胞介素(IL)-6和IL-10的水平，并计算TNF-α/IL-10和IL-6/IL-10的比值。采用RT-PCR及Western blotting技术分别观察RAW 264.7细胞源性泡沫细胞SOCS1和SOCS3 mRNA及蛋白的表达。结果:RAW 264.7细胞源性泡沫细胞组细胞培养液中TNF-α、IL-6和IL-10的水平以及TNF-α/IL-10和IL-6/IL-10的比值均明显高于对照组（control）组。而罗格列酮加入泡沫细胞培养液24 h后，TNF-α、IL-6和IL-10的浓度以及TNF-α/IL-10和IL-6/IL-10的比值均明显低于泡沫细胞组。Control组和泡沫细胞组只有少量SOCS1和SOCS3 mRNA及蛋白的表达，罗格列酮作用于泡沫细胞后SOCS1和SOCS3 mRNA及蛋白的表达均明显高于control组和氧化低密度脂蛋白(ox-LDL)组。结论: 罗格列酮上调泡沫细胞SOCS1和SOCS3的表达，抑制泡沫细胞分泌TNF-α、IL-6和IL-10，调节了泡沫细胞促炎/抗炎反应。

Effects of rosiglitazone on expression of SOCS1/SOCS3 and inflammatory reaction in RAW 264.7 cell-derived foam cells

AIM: To investigate whether perioxisome proliferator-activated receptor γ (PPARγ) ligand rosiglitazone regulates suppressor of cytokine signaling 1 (SOCS1) and SOCS3 expression as well as pro-inflammatory/anti-inflammatory responses in RAW 264.7 cell-derived foam cells. METHODS: The concentrations of TNF-α, IL-6 and IL-10 in the cultured supernatant of RAW 264.7 cell-derived foam cells were detected by ELISA, and the ratios of TNF-α/IL-10 and IL-6/IL-10 were calculated. RT-PCR and Western blotting were used to analyze the effects of rosiglitazone on the expression of SOCS1 and SOCS3 at mRNA and protein levels. RESULTS: The concentrations of TNF-α, IL-6 and IL-10, and ratios of TNF-α/IL-10 and IL-6/IL-10 in foam cell group were obviously higher than those in control group, but the concentrations of the above factors in oxidized low-density lipoprotein (ox-LDL) +rosiglitazone group were apparently lower than those in foam cell group. The expression of SOCS1 and SOCS3 at mRNA and protein levels in oxLDL+rosiglitazone group was apparently higher than that in control and foam cell group. CONCLUSION: PPARγ ligand rosiglitazone up-regulates the expression of SOCS1 and SOCS3 at mRNA and protein levels and regulates the balance of pro-inflammatory/anti-inflammatory responses in RAW 264.7 cell-derived foam cells.