Toll样受体4在宫颈细胞系和宫颈上皮病变中的表达及与HPV16感染的关系

Expression of Toll-like receptor 4 in cervical cell lines and cervical lesions and its relation to HPV16 infection

目的:检测Toll样受体4(Toll-like receptor 4,TLR4)在宫颈细胞系和宫颈病变组织中的表达,探讨TLR4在宫颈病变进展中的作用及与人乳头状瘤病毒(human papillomavirus 16,HPV16)感染的关系。方法:用RT-PCR检测H8,SiHa,Caski细胞中HPV16 E6基因的mRNA含量;Western免疫印迹测定3种细胞系中TLR4蛋白含量;免疫组织化学检测127例慢性宫颈炎、宫颈上皮内瘤变(cervical intra-epithelial neoplasia,CIN)以及宫颈鳞癌病变组织石蜡切片中TLR4蛋白的表达。抽提石蜡组织总DNA,用PCR方法检测组织中HPV16的感染情况。结果:Caski和SiHa细胞中HPV16 E6基因mRNA含量和TLR4蛋白表达明显高于H8正常对照(P<0.05),且Caski细胞中HPV16 E6基因mRNA含量和TLR4蛋白表达也显著高于SiHa细胞(P<0.05);TLR4在慢性子宫颈炎,CIN和宫颈鳞癌组织的表达分别为32.0%,59.4%和77.8%,随着宫颈上皮病变加重TLR4表达增强(P<0.01),并且与宫颈癌分化程度有关(P<0.01);HPV16在宫颈病变组织中的表达随着病理分级逐渐增高,在慢性子宫颈炎、CIN和宫颈鳞癌组织中分别为8.0%,48.4%和81.0%(P<0.01);在CIN和宫颈癌组织中TLR4与HPV16相关(r=0.303,P<0.05;r=0.633,P<0.05)。结论:HPV16感染可以上调TLR4在宫颈上皮病变中的表达,TLR4与HPV16共同作用对宫颈上皮从炎症发展到CIN至宫颈癌过程中发挥重要作用。

Objective：To explore the relation between human papillomavirus （HPV16） infection and expression of Toll-like receptor 4 （TLR4） in cervical cell lines and cervical lesion tissues and to investigate the effect of TLR4 on cervical cancer progression.Methods：Expression of HPV16 E6 mRNA was detected by RT-PCR. Western blot and immunohistochemistry were used to detect the expression of TLR4 in H8, SiHa, Caski cell lines and formalin-ifxed and paraffn-embeded cervical tissue specimens with cervicitis, cervical intra-epithelial neoplasia （CIN） and cervical squamous cell carcinama （CSCC）. DNA was extracted from paraffn-embedded cervical cancer tissues and HPV16 genes were detected. Results：The differentiation expression of HPV16 E6 mRNA and TLR4 in SiHa and Caski was signiifcantly higher than that of normal cervical cell H8 （P0.05）. hTe expression of TLR4 was signiifcantly correlated with HPV16 infection in CIN and CSCC （r=0.303, P Conclusion：High expression of TLR4 may play important roles in the development and progression of CIN and CSCC, and the expression of TLR4 can be up-regulated by HPV16 infection.