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IKKs 参与细胞因子样系统和固有免疫系统抗病毒反应的调节。

IKKs Participate in Regulation of Cytokine-Like System and Antiviral Responses of Innate Immune System.

机构信息

Faculty of Science, Department of Biochemistry, Center of Excellence for Molecular Biology and Genomics of Shrimp, Chulalongkorn University, Bangkok, Thailand.

National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.

出版信息

Front Immunol. 2019 Jun 25;10:1430. doi: 10.3389/fimmu.2019.01430. eCollection 2019.

DOI:10.3389/fimmu.2019.01430
PMID:31293588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6604761/
Abstract

The IKK-NF-κB signaling cascade is one of the crucial responsive mechanisms in inflammatory and immune responses. The key kinase proteins called inhibitor of kappa B kinases (IKKs) serve as the core elements involved in cascade activation. Here, the complete ORFs of IKK homologs, , , and , from the black tiger shrimp were identified and characterized for their functions in shrimp antiviral responses. The transcripts were widely expressed in various examined tissues and the IKKε protein was detected in all three types of shrimp hemocytes. Only the and were responsive to white spot syndrome virus (WSSV), yellow head virus (YHV) and a bacterium infection, while the exhibited no significant response to pathogen infection. On the contrary, suppression of and by dsRNA-mediated RNA interference (RNAi) resulted in a rapid death of WSSV-infected shrimp and the significant reduction of an IFN-like transcript. Whereas, the mRNA levels of the antimicrobial peptides, and , and a transcription factor, were significantly increased, those of , and were unaffected. Overexpression of IKKβ and IKKε in HEK293T cells differentially activated the NF-κB and IFNβ promoter activities, respectively. These results suggest that the IKKβ and IKKε may act as common factors regulating the expression of immune-related genes from various signaling pathways. Interestingly, the IKKs may also contribute a possible role in shrimp cytokine-like system and cross-talking between signaling transductions in innate immune responses.

摘要

IKK-NF-κB 信号级联是炎症和免疫反应中关键的响应机制之一。称为 IκB 激酶 (IKK) 的关键激酶蛋白作为级联激活涉及的核心元件。在这里,从黑虎虾中鉴定并表征了 IKK 同源物 、 、 、和 的完整 ORF,以研究它们在虾抗病毒反应中的功能。 转录本广泛表达于各种检测组织中,IKKε 蛋白存在于三种类型的虾血细胞中。只有 和 对白斑综合征病毒 (WSSV)、黄头病毒 (YHV) 和细菌 感染有反应,而 对病原体感染没有明显反应。相反,通过 dsRNA 介导的 RNA 干扰 (RNAi) 抑制 和 导致 WSSV 感染的虾迅速死亡,IFN 样 转录物的显著减少。然而,抗菌肽 、 、 和 以及转录因子 的 mRNA 水平显著增加, 、 和 的 mRNA 水平不受影响。在 HEK293T 细胞中过表达 IKKβ 和 IKKε 分别差异激活 NF-κB 和 IFNβ 启动子活性。这些结果表明,IKKβ 和 IKKε 可能作为调节来自各种信号通路的免疫相关基因表达的共同因子。有趣的是,IKK 也可能在虾细胞因子样系统和先天免疫反应中信号转导的串扰中发挥作用。

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