SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development

SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development
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SjE16.7激活巨噬细胞并促进日本血吸虫卵诱导的肉芽肿发展

DOI:
10.1016/j.actatropica.2015.05.016
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发表时间:
2015-09-01
期刊:
影响因子:
2.7
通讯作者:
Wang, Zhaojun
Wang, Zhaojun
中科院分区:
医学2区
文献类型:
--
作者:
Fang, Yan;Wu, Chenyun;Wang, Zhaojun

文献摘要

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SjE16.7是来自日本血吸虫的卵特异性蛋白,其募集中性粒细胞并在宿主组织中启动炎性肉芽肿反应。然而,由于巨噬细胞是已知的鸡蛋肉芽肿形成的重要调节器,我们研究了SjE16.7对这种细胞类型的影响。在这里,我们报告说,SjE16.7是一种有效的巨噬细胞激活剂,诱导巨噬细胞趋化性和刺激细胞因子的产生。用SjE16.7处理小鼠原代巨噬细胞导致促炎细胞因子和抗炎细胞因子(IL-10、IL-12、IL-6和TNF-α)的上调,以及促分裂原活化蛋白激酶(MAPK)的磷酸化。此外,SjE16.7处理增加了巨噬细胞表面MHC II类的表达。重要的是,体内阻断SjE16.7可显著降低虫卵诱导的病理,这是由于白细胞浸润减少和肉芽肿大小减小。本研究结果提示SjE16.7是该病的重要致病因子,也是一个潜在的治疗靶点。(C)2015 Elsevier B. V.版权所有。
SjE16.7 is an egg-specific protein from Schistosoma japonicum that recruits neutrophils and initiates an inflammatory granuloma response in host tissue. However, since macrophages are known to be important regulators of egg granuloma formation we investigated the effect of SjE16.7 on this cell type. Here we report that SjE16.7 is a potent macrophage activator, inducing macrophage chemotaxis and stimulating cytokine production. Treatment of murine primary macrophages with SjE16.7 resulted in upregulation of both pro- and anti-inflammatory cytokines (IL-10, IL-12, IL-6 and TNF-alpha), as well as phosphoryladon of mitogen-activated protein kinases (MAPKs). Moreover, SjE16.7 treatment increased MHC Class II expression on the surface of macrophages. Importantly, in vivo blockade of SjE16.7 significantly reduced egg-induced pathology, as a result of decreased leucocyte infiltration and reduced granuloma size. Our results suggest that SjE16.7 is an important pathogenic factor and a potential treatment target for this disease. (C) 2015 Elsevier B.V. All rights reserved.