Schistosoma japonicum soluble egg antigen inhibits TNF--induced IL-34 expression in hepatic stellate cells
Schistosoma japonicum soluble egg antigen inhibits TNF--induced IL-34 expression in hepatic stellate cells
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日本血吸虫可溶性卵抗原抑制TNF诱导的肝星状细胞IL-34表达
DOI：
10.1007/s00436-018-6165-3
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发表时间：
2019-02-01
影响因子：
2
通讯作者：
Duan, Yinong
中科院分区：
文献类型：
--
作者：
Chen, Liuting;Yu, Yang;Duan, Yinong
肝纤维化的特点是肝脏的主要胶原生成细胞，肝星状细胞的活化，并与炎症有关。尽管许多炎症细胞因子的参与已被报道，特别是IL-34最近被确定为肝纤维化发展中的促纤维化因子。前期研究发现血吸虫卵可导致纤维化相关基因的转录下调，基于这一证据，我们试图探究IL-34是否受可溶性卵抗原（soluble egg antigen， SEA）的调控。我们的研究结果证实，SEA在mRNA和蛋白水平上抑制TNF-诱导的IL-34表达。此外，报告基因分析和qPCR实验的结果表明，SEA损害了TNF-触发的NF-B的激活，以及下游基因的转录。更重要的是，SEA降低了TNF-诱导的IB磷酸化和降解，这两个事件是NF-B激活的典型标志。总之，我们的研究结果表明，在肝星状细胞中，SEA损害NF-B的激活，从而抑制TNF-诱导的IL-34表达。这些发现揭示了一个以前未被发现的靶点和信号通路，支持SEA参与肝纤维化，并为指导正在进行的SEA抗纤维化作用的研究提供了新的线索。
Hepatic fibrosis is characterized by the activation of the main collagen-producing cells of the liver, hepatic stellate cells, and is associated with inflammation. Although the involvement of numerous inflammatory cytokines has been reported, IL-34 in particular has recently been identified as a profibrotic factor in the development of hepatic fibrosis. Previous studies have found that schistosome eggs can lead to transcriptional downregulation of fibrosis-associated genes, and based on this evidence, we attempted to investigate whether or not IL-34 is regulated by soluble egg antigen (SEA). Our findings testified that SEA inhibited TNF--induced expression of IL-34 at both the mRNA and protein levels. Furthermore, results from reporter assays and qPCR experiments demonstrated that SEA impaired the activation of NF-B triggered by TNF-, as well as the transcription of downstream genes. More importantly, SEA decreased the phosphorylation and degradation of IB induced by TNF-, two events that are hallmarks of canonical NF-B activation. In conclusion, our results suggest that, in hepatic stellate cells, SEA impairs NF-B activation and thereby inhibits TNF--induced IL-34 expression. These findings reveal a previously unidentified target and signaling pathway that support SEA's involvement in hepatic fibrosis and provide a new clue to guide ongoing research into the anti-fibrotic effects of SEA.