[人乳头瘤病毒16型存在状态与辅助性T细胞17/调节性T细胞细胞因子的相关性研究]

[Correlation study of HPV-16 existential status with Th17/Treg cytokines].

作者信息

Ding Ai-ping, Zhang Yao, Wei Heng, Luo Qing-shuang, Zhang Shu-lan

机构信息

Department of Obstetrics & Gynecology, Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China.

Department of Obstetrics & Gynecology, Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, China. Email:

出版信息

Zhonghua Yi Xue Za Zhi. 2013 Oct 8;93(37):2957-60.

PMID:24401583

Abstract

OBJECTIVE

To explore the relationship between the presence of HPV-16 DNA and the expression Treg surface marker Foxp3(+), peripheral blood levels of Th17/Treg cell-associated cytokines and explore their roles and significance in cervical cancer progression.

METHODS

Between January 2012 and October 2012 at Shengjing Hospital of China Medical University, a total of 142 HPV16 positive patients were divided into cervical cancer (CC, n = 60), cervical intraepithelial neoplasia (CIN, n = 65) and control group (n = 17). Cervical liquid-based cytological (LBC) samples were collected to detect E2 and E6 genes of HPV type 16 using multiple real-time polymerase chain reaction (PCR). E2/E6 ratio was used to evaluate the physical status of HPV-16 DNA in host cell genome. The SP immunohistochemical method was used to detect the expressions of FOXP3 in cervical lesions. The concentrations of Th17/Treg cell-associated cytokines were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Under the same status of HPV16 DNA in vivo, the levels of Foxp3(+), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were significantly higher than those of the control group (P < 0.01) while the levels of interleukin-17 (IL-17) and interleukin-21 (IL-21)were significantly lower than those of the control group (P < 0.05) . In the same disease, HPV16 DNA integration rate grew with the increases of Foxp3(+), TGF-β and IL-10 while IL-17 and IL-21 were opposite. In the different status of HPV16 type DNA, the expression of Foxp3(+) was closely correlated with Federation International of Gynecology and Obstetrics (FIGO) stage, histological grade and lymphnode metastasis (P < 0.05) except for age (P > 0.05).

CONCLUSION

Treg cytokines, HPV16 integration rate and severity of cervical lesions are positively correlated while Th17 cytokines show opposite effects. Th17/Treg cell-associated cytokines may play an important role in the occurrence and development of cervical cancer.

摘要

目的

探讨人乳头瘤病毒16型（HPV-16）DNA的存在与调节性T细胞（Treg）表面标志物叉头状转录因子3（Foxp3）（+）的表达、外周血中辅助性T细胞17（Th17）/Treg细胞相关细胞因子水平之间的关系，并探讨它们在宫颈癌进展中的作用及意义。

方法

2012年1月至2012年10月在中国医科大学附属盛京医院，共142例HPV16阳性患者被分为宫颈癌组（CC，n = 60）、宫颈上皮内瘤变组（CIN，n = 65）和对照组（n = 17）。收集宫颈液基细胞学（LBC）样本，采用多重实时聚合酶链反应（PCR）检测16型HPV的E2和E6基因。E2/E6比值用于评估HPV-16 DNA在宿主细胞基因组中的物理状态。采用SP免疫组织化学方法检测宫颈病变中FOXP3的表达。采用酶联免疫吸附测定（ELISA）法检测Th17/Treg细胞相关细胞因子的浓度。

结果

在体内HPV16 DNA处于相同状态下，Foxp3（+）、转化生长因子-β（TGF-β）和白细胞介素-10（IL-10）水平显著高于对照组（P < 0.01），而白细胞介素-17（IL-17）和白细胞介素-21（IL-21）水平显著低于对照组（P < 0.05）。在同一疾病中，HPV16 DNA整合率随Foxp3（+）、TGF-β和IL-10的升高而升高，而与IL-17和IL-21的变化相反。在HPV16型DNA的不同状态下，Foxp3（+）的表达与国际妇产科联盟（FIGO）分期、组织学分级和淋巴结转移密切相关（P < 0.05），但与年龄无关（P > 0.05）。