幽门螺杆菌相关毒力因子 CAGA 影响消化性溃疡患者外周血单个核细胞趋化因子 CXCL10、CCL17、CCL20、CCL22 及其受体的表达。

THE H. PYLORI-RELATED VIRULENCE FACTOR CAGA INFLUENCES THE EXPRESSION OF CHEMOKINES CXCL10, CCL17, CCL20, CCL22, AND THEIR RECEPTORS BY PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PEPTIC ULCER PATIENTS.

机构信息

Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Department of Internal Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Arq Gastroenterol. 2020 Oct-Dec;57(4):366-374. doi: 10.1590/S0004-2803.202000000-70.

DOI:10.1590/S0004-2803.202000000-70

PMID:33331471

Abstract

BACKGROUND

During the Helicobacter pylori (HP) infection, the infiltration of the leukocytes into stomach mucosa is directed by locally produced chemokines that play a decisive role in infection outcome. The CagA is the most potent virulence factor of HP, so that the infection with CagA + strains is associated with more severe complications than infection with CagA - HP.

OBJECTIVE

The aim was to determine the expression of chemokines CXCL10, CCL17, CCL20 and CCL22, and their receptors by CagA + HP- and CagA - HP-derived crude extract (HP-CE)-stimulated peripheral blood mononuclear cells (PBMCs) from peptic ulcer (PU) patients.

METHODS

The serum and the PBMCs were collected from 20 HP-infected PU patients, 20 HP-infected asymptomatic subjects (HIA) and 20 non-infected healthy subjects (NHS). The PBMCs were cultured in absence of stimulator or with 10 µg CagA + HP crude extract (CagA + CE), 10 µg CagA - HP crude extract (CagA - CE). Chemokines and receptors were measured by ELISA and real time-PCR respectively.

RESULTS

In PU patients, the production of chemokines CXCL10, CCL17, CCL20 and CCL22, and the expression of chemokine receptors CXCR3, CCR4 and CCR6 by CagA + CE-induced PBMCs were significantly higher than non-stimulated and CagA - CE stimulated cultures. The CXCL10 production by CagA + CE stimulated PBMCs from HIA subjects was significantly higher than the equal cultures from PU and NHS groups. The CCL17 and the CCL20 production by non-stimulated, CagA + CE stimulated, and CagA - CE stimulated PBMCs from PU subjects were significantly higher than the equal cultures from NHS and HIA groups. The CCL22 production by non-stimulated, CagA + CE stimulated and CagA - CE stimulated PBMCs from NHS group were significantly higher than the equal cultures from HIA and PU groups. The CagA + CE stimulated PBMCs from HIA subjects expressed lower amounts of CCR6 in comparison with CagA + CE stimulated PBMCs from NHS and PU groups. The serum levels CXCL10 and CCL20 in PU and HIA groups were significantly higher than NHS subjects. NHS and HIA groups displayed higher serum levels of CCL22 in comparison with PU patients.

CONCLUSION

Results indicated that the CagA status of bacterium influence the expression of chemokines and receptors by HP-CE stimulated PBMCs from PU patients.

摘要

背景

在幽门螺杆菌（HP）感染期间，白细胞浸润胃黏膜是由局部产生的趋化因子所引导的，这些趋化因子在感染结果中起着决定性作用。CagA 是 HP 最有效的毒力因子，因此感染 CagA+菌株比感染 CagA- HP 与更严重的并发症相关。

目的

本研究旨在确定 CagA+HP 和 CagA-HP 来源的粗提取物（HP-CE）刺激消化性溃疡（PU）患者外周血单个核细胞（PBMC）后趋化因子 CXCL10、CCL17、CCL20 和 CCL22 及其受体的表达情况。

方法

从 20 名 HP 感染的 PU 患者、20 名 HP 感染无症状个体（HIA）和 20 名非感染健康个体（NHS）中收集血清和 PBMC。将 PBMC 在无刺激物或 10µg CagA+HP 粗提取物（CagA+CE）、10µg CagA-HP 粗提取物（CagA-CE）存在下培养。通过 ELISA 和实时 PCR 分别测量趋化因子和受体。

结果

在 PU 患者中，CagA+CE 诱导的 PBMC 产生的趋化因子 CXCL10、CCL17、CCL20 和 CCL22 以及趋化因子受体 CXCR3、CCR4 和 CCR6 的表达明显高于非刺激和 CagA-CE 刺激的培养物。HIA 患者的 CagA+CE 刺激的 PBMC 产生的 CXCL10 明显高于 PU 和 NHS 组的等量培养物。非刺激、CagA+CE 刺激和 CagA-CE 刺激的 PU 患者的 PBMC 产生的 CCL17 和 CCL20 明显高于 NHS 和 HIA 组的等量培养物。非刺激、CagA+CE 刺激和 CagA-CE 刺激的 NHS 组的 PBMC 产生的 CCL22 明显高于 HIA 和 PU 组的等量培养物。与 NHS 和 PU 组的 CagA+CE 刺激的 PBMC 相比，HIA 组的 CagA+CE 刺激的 PBMC 表达的 CCR6 量较低。PU 和 HIA 组的血清 CXCL10 和 CCL20 水平明显高于 NHS 组。与 PU 患者相比，NHS 和 HIA 组的血清 CCL22 水平更高。