Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in Toxoplasma gondii-Infected THP-1 Macrophages.

Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in Toxoplasma gondii-Infected THP-1 Macrophages.
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IL-1β 和炎症小体的产生与弓形虫感染的 THP-1 巨噬细胞中 NOD 样受体相关基因的表达上调

DOI:
10.3347/kjp.2016.54.6.711
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发表时间:
2016-12
期刊:
The Korean journal of parasitology
影响因子:
--
通讯作者:
Quan JH
Quan JH
中科院分区:
其他
文献类型:
--
作者:
Chu JQ;Shi G;Fan YM;Choi IW;Cha GH;Zhou Y;Lee YH;Quan JH

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弓形虫是一种专性细胞内寄生虫,可刺激产生高水平的促炎细胞因子,这对先天免疫很重要。NLR,即,核苷酸结合寡聚化结构域(NOD)样受体作为先天性免疫传感器发挥关键作用,并形成称为炎性体的多蛋白复合物,其介导IL-1β前体的caspase-1依赖性加工。阐明炎性小体成分在T.感染的THP-1巨噬细胞,我们检测了炎性小体相关基因的表达和炎性小体调节细胞因子IL-1β分泌的机制。结果显示T.弓形虫感染T.弓形虫感染还以时间依赖性方式上调炎性小体传感器的表达,包括NLRP 1、NLRP 3、NLRC 4、NLRP 6、NLRP 8、NLRP 13、AIM 2和NAIP。感染还上调炎性小体衔接蛋白ASC和caspase-1 mRNA水平。本研究发现,T.弓形虫感染调节THP-1巨噬细胞中NLRC 4、NLRP 6、NLRP 8、NLRP 13、AIM 2和神经元凋亡抑制蛋白(NAIP)基因的表达,并且炎性小体相关基因的作用可能是介导对T.弓形虫感染
Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion. The results revealed a significant upregulation of IL-1β after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.