Regulation of cytokine expression in murine macrophages stimulated by excretory/secretory products from Trichinella spiralis in vitro
Regulation of cytokine expression in murine macrophages stimulated by excretory/secretory products from Trichinella spiralis in vitro
复制标题
体外旋毛虫排泄/分泌产物刺激小鼠巨噬细胞细胞因子表达的调节
DOI：
10.1007/s11010-011-1046-4
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发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Liu, Mingyuan
中科院分区：
文献类型：
--
作者：
Bai, Xue;Wu, Xiuping;Liu, Mingyuan
旋毛虫是一种人畜共患线虫和食源性寄生虫，感染旋毛虫会导致宿主免疫反应抑制和其他免疫病理改变。旋毛虫的排泄/分泌产物在免疫调节过程中起着重要作用。然而，其机制和相关分子尚不清楚。巨噬细胞是寄生虫免疫调节的靶细胞，在启动和调节宿主对寄生虫感染的免疫反应中起着关键作用。在这项研究中，我们检测了旋毛虫不同阶段的ES产物对J774A.1巨噬细胞活性的调节作用。旋毛虫不同发育阶段的ES产物可降低巨噬细胞表达致炎细胞因子(肿瘤坏死因子α、白介素1β、白介素6和白介素12)的能力。然而，只有3日龄成虫和5日龄成虫/新生幼虫的ES产物显著抑制内毒素诱导的巨噬细胞诱导型一氧化氮合酶基因的表达。此外，ES产品单独作用可增强J774A.1巨噬细胞抗炎细胞因子IL-10、转化生长因子-β和效应分子精氨酸酶1的表达。信号转导研究表明，ES产物显著抑制κB核转位和胞外信号调节蛋白激酶1/2和p38丝裂原活化蛋白激酶的磷酸化。这些结果表明，ES产物通过抑制促炎细胞因子的产生和诱导巨噬细胞向另一种表型转变，在巨噬细胞水平上调节宿主的免疫反应，这可能对蠕虫的生存和宿主的健康至关重要。
Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. The excretory/secretory (ES) products of T. spiralis play important roles in the process of immunomodulation. However, the mechanisms and related molecules are unknown. Macrophages, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite infection. In this study, we examined the effect of ES products from different stages of T. spiralis on modulating J774A.1 macrophage activities. ES products from different stages of T. spiralis reduced the capacity of macrophages to express pro-inflammatory cytokines (tumor necrosis factor α, interleukin-1β , interleukin-6 , and interleukin-12) in response to lipopolysaccharide (LPS) challenge. However, only ES products from 3-day-old adult worms and 5-day-old adult worms/new-born larvae significantly inhibited inducible nitric oxide synthase gene expression in LPS-induced macrophages. In addition, ES products alone boosted the expression of anti-inflammatory cytokines interleukin-10 and transforming growth factor-β and effector molecule arginase 1 in J774A.1 macrophages. Signal transduction studies showed that ES products significantly inhibited nuclear factor-κB translocation into the nucleus and the phosphorylation of both extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase in LPS-stimulated J774A.1 macrophages. These results suggest that ES products regulate host immune response at the macrophage level through inhibition of pro-inflammatory cytokines production and induction of macrophage toward the alternative phenotype, which maybe important for worm survival and host health.