PPARγ激动剂对T细胞增殖及破骨细胞形成的影响  

Inhibition of T cell proliferation and T cell-induced osteoclastogenesis by peroxisome proliferator activated receptor-γ ligand

作　　者：林晓萍[1,2,3] 刘洪利[1] 杜莉莉[1] Toshihisa Kawai 张春辉[1] 

机构地区：[1]中国医科大学附属盛京医院口腔科,辽宁沈阳110004 [2]辽宁省口腔医学研究所牙周病研究室,辽宁沈阳110001 [3]Department of Immunology,The Forsyth Institute

出　　处：《上海口腔医学》2011年第4期347-351,共5页Shanghai Journal of Stomatology

基　　金：辽宁省自然科学基金(20092139);沈阳市科学技术项目计划(F10-149-9-32)

摘　　要：目的:观察过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor-γ,PPARγ)激动剂15d-PGJ2对小鼠T细胞增殖、T细胞分泌的细胞因子表达及破骨样细胞形成的影响,并探讨其可能的作用机制。方法:体外分离伴放线放线杆菌(A.actinomycetetemcomitans,Aa)免疫的BALB/c小鼠颈部淋巴细胞,提取T细胞进行体外扩增,分别加入浓度为0、1×10-8、1×10-7,1×10-6,1×10-5mol/L的15d-PGJ2进行干预。培养3d后,3H-Tdr掺入法测定T细胞的增殖反应;ELISA法测定细胞上清中核因子-κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)、TNF-α和IL-10的表达水平;取扩增的T细胞上清与RAW 264.7细胞共同培养后,抗酒石酸酸性磷酸酶染色(tartrate resistant acid phosphatase,TRAP)测定破骨样细胞的形成。采用SPSS 11.0软件包对数据进行统计学分析。结果:以1×10-5mol/L 15d-PGJ2处理的小鼠T细胞3d后,与对照组相比,T细胞增殖显著受抑;上清中RANKL、TNF-α的表达水平下降,IL-10无显著变化;TRAP染色阳性细胞数减少,具有统计学意义(P<0.05),且呈浓度依赖性。结论:PPARγ激动剂15d-PGJ2可抑制T细胞增殖,减少炎性因子分泌,降低破骨样细胞的形成,提示PPARγ配体在抑制T细胞诱导的骨吸收方面发挥积极作用。PURPOSE： To examine the effect of peroxisome proliferator activated receptor-γ（PPARγ） ligand,15d-PGJ2 on inhibition of T cell proliferation and T cell-mediated osteoclastogenesis,and clarify the possible mechanism.METHODS： T cells from A.actinomycetetemcomitans immunized BALB/c mice were isolated from cervical lymph nodes and T lymphocytes enriched in vitro.At 3-day after 15d-PGJ2（0,1×10^-8,1×10^-7,1×10^-6,1×10^-5mol/L） induction,T cell proliferation analysis was measured by cintilography,the concentration of RANKL,TNF-α and IL-10 were measured in culture supernatants by ELISA,and osteoclastogenesis of co-culture with RAW 264.7 cell and T lymphocyte supernatants that enriched in vitro by tartrate resistant acid phosphatase（TRAP） staining.SASS 11.0 software package was used for statistical analysis.RESULTS： By 1×10^-5mol/L 15d-PGJ2 induction,T cell 3H incorporation remarkably decreased,the expression of RANKL and TNF-α in the supernatant markedly decreased,significantly different compared with the control group（P〈0.05）,but IL-10 was not significantly different,and the numbers of TRAP positive cells decreased,significantly different compared with the control group（P〈0.05）,which was dose-dependent.CONCLUSIONS： PPARγ ligand 15d-PGJ2 can inhibit 3H incorporation,down-regulate cytokine release,decrease T cell-induced osteoclastogenesis.The data suggest that PPARγ ligand plays an important role in T cell-induced bone resorption.Supported by Natural Science Foundation of Liaoning Province（20092139） and Research Fund of Science and Technology Commission of Shenyang City（F10^-149-9-32）.

关 键 词：过氧化物酶体增殖物激活受体Γ 细胞因子 破骨细胞形成 伴放线放线杆菌 T淋巴细胞 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]