TLR2和TLR4在牛型结核分枝杆菌诱导的肾小管上皮细胞损伤中的作用

Role of TLR2 and TLR4 in Mycobacterium bovis Bacillus CalmetteGuérin-induced injury in renal tubule epithelial cells

目的:探讨Toll样受体(TLR)2和TLR4在牛型结核分枝杆菌卡介苗(BCG)诱导的人肾小管上皮细胞(HK-2细胞)损伤中的作用。方法:用BCG刺激HK-2细胞,通过荧光定量PCR和Western blotting方法分别检测TLR2、TLR4、转化生长因子β1(TGF-β1)和趋化因子CX3CL1的表达。将TLR2抗体和TLR4拮抗剂CLI-90分别与BCG共刺激HK-2细胞,通过荧光定量PCR和Western blotting方法分别检测TGF-β1和CX3CL1的表达水平。结果:BCG刺激HK-2细胞可诱导TLR2、TLR4、TGF-β1和CX3CL1表达上调,TLR2抗体和TLR4拮抗剂可部分抑制BCG引起的TGF-β1和CX3CL1表达上调。结论:BCG可通过激活TLR2和TLR4引起TGF-β1和CX3CL1表达上调,提示TLR2和TLR4介导的信号通路在结核分枝杆菌致肾小管上皮细胞损伤中发挥重要作用。

AIM：To explore the effect of Toll-like receptor （ TLR） 2 and TLR4 in Mycobacterium bovis Bacillus Calmette-Guerin （BCG）-induced human proximal renal tubule epithelial cell （HK-2） injury.METHODS：HK-2 cells were stimulated by BCG, and the expression of TLR2, TLR4, chemokine （C-X3-C motif） ligand 1 （CX3CL1） and transforming growth factor beta 1 （ TGF-β1 ） was detected by quantitative real-time PCR and Western blotting .TLR2 monoclonal antibody and TLR4 inhibitor were used to treat the HK-2 cells 1 h before BCG stimulation.The expression of CX3CL1 and TGF-β1 was evaluated by quantitative real-time PCR and Western blotting .RESULTS： BCG increased the expression of TLR2, TLR4, CX3CL1 and TGF-β1 in the HK-2 cells.Additionally, the expression of CX3CL1 and TGF-β1 was inhibited partly by TLR2 monoclonal antibody or TLR4 inhibitor.CONCLUSION：BCG is able to increase the production of TLR 2, TLR4, CX3CL1 and TGF-β1 in the HK-2 cells.TLR2 and TLR4 signaling pathways play important roles in tubule epitheli-al cell injury induced by BCG .