IκBα phosphorylation and associated NF-κB activation are essential events in lymphocyte activation, proliferation, and anti-bacterial adaptive immune response of Nile tilapia
IκBα phosphorylation and associated NF-κB activation are essential events in lymphocyte activation, proliferation, and anti-bacterial adaptive immune response of Nile tilapia
复制标题
I kappa B α 磷酸化和相关的 NF-kappa B 激活是尼罗罗非鱼淋巴细胞激活、增殖和抗菌适应性免疫反应中的重要事件
DOI：
10.1016/j.dci.2019.103526
复制
发表时间：
2020-02-01
影响因子：
2.9
通讯作者：
Yang, Jialong
中科院分区：
文献类型：
--
作者：
Li, Cheng;Yu, Junkun;Yang, Jialong
抑制性蛋白 I kappa B α 通过调节转录因子 NF-kappa B 的活性，在炎症过程和免疫反应中发挥着至关重要的作用。在硬骨鱼中，先天免疫的 NF-kappa B 信号传导已取得了巨大进展，但该通路是否调节适应性免疫以及如何调节仍不清楚。在本研究中，在描述了尼罗罗非鱼 Oreochromis niloticus I kappa B α（定义为 On-I kappa B α）的序列、结构和系统发育特征后，我们研究了 I kappa B α 调节的 NF-kappa B 激活与尼罗罗非鱼淋巴细胞介导的适应性免疫反应之间的关联。我们发现On-I kappa B α在进化上是保守的，其mRNA在多种组织中广泛表达，其中在躯干肾中表达最多。嗜水气单胞菌感染后，在先天免疫和适应性免疫阶段，脾脏中 On-I kappa B α 的 mRNA 表达显着上调。此外，在嗜水气单胞菌感染后3、5或8天，脾白细胞中On-I kappa B α和下游On NF-kappa B p65的磷酸化明显升高，表明NF-kappa B信号传导被激活。与增强的蛋白质磷酸化相关，白细胞增殖在同一免疫阶段增强，表明 I kappa B α 和 I kappa B α 调节的 NF-kappa B 信号在初级适应性免疫反应中存在潜在关联。尽管 T 细胞特异性有丝分裂原 PHA 激活淋巴细胞并没有显着改变 On-I kappa B α mRNA 表达，但激动剂 PMA 激活淋巴细胞明显升高脾白细胞中 On-I kappa B α 和 OnNF-4:13 p65 磷酸化。总之，结果表明 IxBa 磷酸化及其调节的 NF-κ B 激活是与尼罗罗非鱼淋巴细胞激活、增殖和抗菌适应性免疫反应相关的重要事件。我们的研究有助于了解硬骨鱼适应性免疫的调节机制。
Inhibitory protein I kappa B alpha plays a crucial role in the inflammatory process and immune response by regulating the activity of transcription factor NF-kappa B. In teleost, great progress has been achieved regarding NF-kappa B signaling for innate immunity, but whether this pathway modulates adaptive immunity, and how, remains largely unclear. In this study, after characterizing the sequence, structure, and phylogeny of Nile tilapia Oreochromis niloticus I kappa B alpha (defined as On-I kappa B alpha), we investigated the association between I kappa B alpha-regulated NF-kappa B activation and the lymphocyte-mediated adaptive immune response in Nile tilapia. We found that On-I kappa B alpha was evolutionarily conserved, and its mRNA was expressed widely in various tissues, with most abundance in the trunk kidney. mRNA expression of On-I kappa B alpha was significantly upregulated in spleen at both innate and adaptive immune stages after Aeromonas hydrophila infection. Moreover, phosphorylation of On-I kappa B alpha and the downstream On NF-kappa B p65 was obviously elevated in spleen leukocytes at 3, 5, or 8 days after A. hydrophila infection, indicating the activation of NF-kappa B signaling. Correlating with the augmented protein phosphorylation, leukocyte proliferation was enhanced during the same immune stage, suggesting the potential association of I kappa B alpha and I kappa B alpha-regulated NF-kappa B signaling in the primary adaptive immune response. Although lymphocyte activation by the T cell-specific mitogen PHA did not alter On-I kappa B alpha mRNA expression significantly, lymphocyte activation by the agonist PMA obviously elevated On-I kappa B alpha and OnNF-4:13 p65 phosphorylation in spleen leukocytes. Together, the results suggest that IxBa phosphorylation and its regulated NF-kappa B activation are essential events associated with lymphocyte activation, proliferation, and anti-bacterial adaptive immune response in Nile tilapia. Our study aids to understand the regulatory mechanism of adaptive immunity in teleost.