Gene expression profile of LPS-stimulated dendritic cells induced by a recombinant Sj16 (rSj16) derived from Schistosoma japonicum
Gene expression profile of LPS-stimulated dendritic cells induced by a recombinant Sj16 (rSj16) derived from Schistosoma japonicum
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日本血吸虫重组 Sj16 (rSj16) 诱导的 LPS 刺激树突状细胞的基因表达谱
DOI：
10.1007/s00436-014-3973-y
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发表时间：
2014-06
影响因子：
2
通讯作者：
Sun, Xi
中科院分区：
文献类型：
--
作者：
Lv, Zhiyue;Fung, Mingchiu;Wu, Zhongdao;Sun, Xi
Sj16是日本血吸虫分泌的一种16 kDa蛋白，已在体外和体内证明具有抗炎作用，但其机制仍不清楚。在本研究中，进行了微阵列分析，以研究重组 Sj16 (rSj16) 对脂多糖 (LPS) 刺激的树突状细胞 (DC) 基因表达的影响。用 LPS、LPS + 重组 Sj16 (rSj16) 或单独的 rSj16 处理未成熟 DC 24 小时，并使用互补 DNA (cDNA) 微阵列检查基因表达谱。以表达变化2倍为截止值，添加rSj16后，509个基因受到影响，226个基因上调，283个基因下调。功能注释聚类工具分析表明，rSj16影响的基因主要与炎症反应、防御反应、免疫系统过程调节、细胞凋亡和细胞迁移相关。结果显示，rSj16 减少了 LPS 诱导的促炎基因，如细胞因子（例如 IL6、IL18、IFN-γ、IL12a、IL1b）、趋化因子和受体（例如 CXCL1、CXCL9、CCL5、CCR5、CCR1、CCR2、CXCR3），并增加了抗炎基因 IL-10。通过通路分析进一步对这些基因进行数据挖掘表明，rSj16调控的基因显着参与细胞因子-细胞因子受体相互作用、NOD样受体信号通路、Toll样受体信号通路、抗原加工和呈递以及Jak-STAT信号通路。此外，实时定量PCR（qRT-PCR）和Western blot分析表明，rSj16下调核因子κ-β激酶亚基β抑制剂（IKKβ）和核因子κβ p65（NF-κβ）信使RNA（mRNA）的表达，并抑制IKKβ和NF-κB p65蛋白的磷酸化，这表明rSj16通过抑制NF-κB 信号通路。这些结果为进一步了解Sj16的免疫调节机制提供了有用的信息，表明Sj16可以作为免疫抑制剂药物开发的潜在分子。
Sj16, a 16-kDa protein secreted from Schistosoma japonicum, has been demonstrated an anti-inflammatory effect in vitro and in vivo, but its mechanism is still not clear. In this study, microarray analysis was performed to investigate the effects of recombinant Sj16 (rSj16) on the gene expression of the lipopolysaccharide (LPS)-stimulated dendritic cells (DCs). Immature DCs were treated with LPS, LPS + recombinant Sj16 (rSj16), or rSj16 alone for 24 h, and the gene expression profiles were examined using complementary DNA (cDNA) microarrays. With the cutoff value of 2-fold change in the expression, 509 genes were affected, 226 genes upregulated, and 283 genes downregulated after adding rSj16. Analysis by functional annotation clustering tool showed that rSj16-affected genes mainly associated with inflammatory response, defense response, regulation of immune system process, apoptosis, and cell migration. The results revealed that rSj16 reduced the LPS-induced pro-inflammatory genes such as cytokines (e.g., IL6, IL18, IFN-γ, IL12a, IL1b), chemokines, and receptors (e.g., CXCL1, CXCL9, CCL5, CCR5, CCR1, CCR2, CXCR3) and increased the anti-inflammatory gene IL-10. Further data mining of these genes by pathway analysis showed that genes regulated by rSj16 were significantly involved in cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, antigen processing and presentation, and Jak-STAT signaling pathway. In addition, quantitative real-time PCR (qRT-PCR) and Western blot analysis showed that rSj16 downregulated the expression of inhibitor of nuclear factor kappa-β kinase subunit beta (IKKβ) and nuclear factor-kappa β p65 (NF-κβ) messenger RNA (mRNA) and inhibited the phosphorylation of IKKβ and the NF-κB p65 protein, which implied that rSj16 exerting immunomodulatory effects by suppressing NF-κB signaling pathway. These results provide useful information in further understanding of the immunoregulation mechanisms of Sj16, and it is indicated that Sj16 could be as a potential molecule for the immunosuppressant drug development.
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