GW1929对氧化型低密度脂蛋白诱导巨噬细胞SOCS1和SOCS3表达及炎症反应的影响  

Effects of GW1929 on Macrophage SOCS1/SOCS3 Expression and Inflammatory Reaction Induced by Oxidized Low Density Lipoprotein

作　　者：李飞[1] 袁勇[1] 董剑廷[1] 冯力[1] 邓志华[1] 韩莹[1] 

机构地区：[1]中山市人民医院心血管内科,广东省中山市528400

出　　处：《中国动脉硬化杂志》2013年第3期233-237,共5页Chinese Journal of Arteriosclerosis

摘　　要：目的观察过氧化体增殖物激活型受体γ(PPARγ)激动剂GW1929对氧化型低密度脂蛋白(ox-LDL)诱导巨噬细胞SOCS1、SOCS3表达和肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)、γ干扰素(IFN-γ)生成的影响。方法 ox-LDL(50 mg/L)、GW1929(20μmol/L)作用于小鼠腹腔巨噬细胞4 h后,采用Real-time PCR技术观察各组SOCS1及SOCS3 mRNA的表达。采用Western blot技术观察ox-LDL作用于小鼠腹腔巨噬细胞6 h后,SOCS1及SOCS3蛋白的表达。最后ELISA法测定ox-LDL作用于小鼠腹腔巨噬细胞24 h后,各组培养液上清中TNF-α、IL-10、IFN-γ的浓度。结果 ox-LDL组巨噬细胞SOCS1及SOCS3 mRNA和蛋白的表达明显高于对照组与GW1929组(P<0.05),而ox-LDL+GW1929组SOCS1的表达明显高于ox-LDL组(P<0.05),SOCS3的表达却明显低于ox-LDL组(P<0.05)。ox-LDL组细胞培养液中TNF-α、IFN-γ及IL-10的浓度以及TNF-α/IL-10、IFN-γ/IL-10比值均明显高于对照组及GW1929组(P<0.05),加入GW1929 24 h后培养液中TNF-α、IFN-γ及IL-10的浓度以及TNF-α/IL-10、IFN-γ/IL-10比值均明显低于ox-LDL组(P<0.05)。结论 ox-LDL促进了小鼠腹腔巨噬细胞SOCS1和SOCS3 mRNA及蛋白的表达增多,而PPARγ激动剂可能通过进一步上调SOCS1而不是SOCS3的表达,以对抗过度的炎症反应,调节促炎/抗炎反应的平衡。Aim To investigate whether peroxisome proliferator activated receptors gamma （PPARγ） activator GW1929 regulates suppressors of cytokine signaling-1 （SOCS1） and SOCS3 expression as well as production of tumor necrosis factorα （TNF-α）, interleukin-10 （IL-10）, and interferon-γ （IFN-γ） in macrophages induced by oxidized low density lipoprotein （ox-LDL）. Methods Real-time PCR were used to analyze SOCS1 and SOCS3 mRNA expression after the mouse peritoneal macrophages were pretreated with ox-LDL （50 mg/L） and GW1929 （20 μmol/L） for 4 h. Western blot were used to analyze SOCS1 and SOCS3 protein expression after the mouse peritoneal macrophages were pretreated with ox-LDL （50 mg/L） and GW1929 （20 μmol/L） for 6 h. The concentrations of TNF-α, IL-10 and IFN-γ in the culture supernatant were detected after macrophages were pretreated with ox-LDL and GW1929 for 24 h by enzyme linked immunosorbent assay （ELISA）. Results The concentrations of TNF-α, IL-10 and IFN-γ and ratios of TNF-α/IL-10,IFN-γ/IL-10 in ox-LDL group were higher than those in control and GW1929 group obviously, but the concentrations of the above factors in ox-LDL ＋GW1929 group were lower than those in ox-LDL group apparently. The expressions of SOCS1 at mRNA and protein level in ox-LDL group were higher than those in control and GW1929 group obviously,and SOCS1 expression in ox-LDL ＋ GW1929 group was higher than that in ox-LDL group, but SOCS3 expression in ox- LDL ＋ GW1929 group was lower than that in ox-LDL group. Conclusion PPARy/ activator GW1929 up- regulates the expressions of SOCS1 but not SOCS3 at mRNA and protein level and regulates the balance of pro-inflammatory /anti-inflammatory reactions in maerophages induced by ox-LD.

关 键 词：动脉粥样硬化 炎症反应 细胞因子 细胞因子信号抑制剂 巨噬细胞 过氧化体增殖物激活 型受体 

分 类 号：R363[医药卫生—病理学]