[Toll样受体4在宫颈细胞系和宫颈病变中的表达及其与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].

作者信息

Li Qiaozhi, Ayshamgul Hasimu, Jiang Yan, Liu Yanhong, Li Guancheng

机构信息

Department of Pathology, Xinjiang Medical University, Urumqi 830011; Cancer Research Institute, Central South University, Changsha 410078, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Nov;38(11):1110-6. doi: 10.3969/j.issn.1672-7347.2013.11.005.

DOI:10.3969/j.issn.1672-7347.2013.11.005

PMID:24316922

Abstract

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-fixed and paraffin-embedded cervical tissue specimens with cervicitis, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinama (CSCC). DNA was extracted from paraffin-embedded cervical cancer tissues and HPV16 genes were detected.

RESULTS

The differentiation expression of HPV16 E6 mRNA and TLR4 in SiHa and Caski was significantly higher than that of normal cervical cell H8 (P<0.05). The positive expression rates of TLR4 and HPV16 in chronic cervicitis, CIN, and cervical cancer were 32.0%, 59.4%, and 77.8% (P<0.01) and 8.0%, 48.4%, and 81.0% (P<0.01), respectively. Up-regulation of TLR4 was correlated with tumor differentiation (P<0.01), but not with FIGO stages or lymph node metastasis (P>0.05). The expression of TLR4 was significantly correlated with HPV16 infection in CIN and CSCC (r=0.303, P<0.05, r=0.633, P<0.05).

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.

摘要

目的

探讨人乳头瘤病毒（HPV16）感染与宫颈细胞系及宫颈病变组织中Toll样受体4（TLR4）表达的关系，并研究TLR4对宫颈癌进展的影响。

方法

采用RT-PCR检测HPV16 E6 mRNA的表达。运用蛋白质免疫印迹法和免疫组织化学法检测H8、SiHa、Caski细胞系以及伴有宫颈炎、宫颈上皮内瘤变（CIN）和宫颈鳞状细胞癌（CSCC）的福尔马林固定石蜡包埋宫颈组织标本中TLR4的表达。从石蜡包埋的宫颈癌组织中提取DNA并检测HPV16基因。

结果

SiHa和Caski中HPV16 E6 mRNA和TLR4的差异表达显著高于正常宫颈细胞H8（P<0.05）。TLR4和HPV16在慢性宫颈炎、CIN和宫颈癌中的阳性表达率分别为32.0%、59.4%和77.8%（P<0.01）以及8.0%、48.4%和81.0%（P<0.01）。TLR4的上调与肿瘤分化相关（P<0.01），但与国际妇产科联盟（FIGO）分期或淋巴结转移无关（P>0.05）。在CIN和CSCC中，TLR4的表达与HPV16感染显著相关（r=0.303，P<0.05，r=0.633，P<0.05）。