Istituto di Calcolo e Reti ad Alte Prestazioni-Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy.
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche-Università di Palermo, Via Archirafi 18, 90128 Palermo, Italy.
Int J Mol Sci. 2023 Feb 18;24(4):4112. doi: 10.3390/ijms24044112.
The Ascidian is a powerful model for studying innate immunity. LPS induction activates inflammatory-like reactions in the pharynx and the expression of several innate immune genes in granulocyte hemocytes such as cytokines, for instance, macrophage migration inhibitory factors (CrMifs). This leads to intracellular signaling involving the Nf-kB signaling cascade that triggers downstream pro-inflammatory gene expression. In mammals, the COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) complex also results in the activation of the NF-kB pathway. It is a highly conserved complex in vertebrates, mainly engaged in proteasome degradation which is essential for maintaining processes such as cell cycle, DNA repair, and differentiation. In the present study, we used bioinformatics and in-silico analyses combined with an in-vivo LPS exposure strategy, next-generation sequencing (NGS), and qRT-PCR to elucidate molecules and the temporal dynamics of Mif cytokines, Csn signaling components, and the Nf-κB signaling pathway in . A qRT-PCR analysis of immune genes selected from transcriptome data revealed a biphasic activation of the inflammatory response. A phylogenetic and STRING analysis indicated an evolutionarily conserved functional link between the Mif-Csn-Nf-kB axis in ascidian during LPS-mediated inflammation response, finely regulated by non-coding molecules such as microRNAs (miRNAs).
海鞘是研究先天免疫的有力模型。LPS 诱导在咽部引发炎症样反应，并在粒细胞血细胞（如细胞因子）中表达几种先天免疫基因，例如巨噬细胞迁移抑制因子（CrMifs）。这导致涉及 NF-kB 信号级联的细胞内信号转导，触发下游促炎基因表达。在哺乳动物中，COP9（组成型光形态发生 9）信号小体（CSN）复合物也导致 NF-kB 途径的激活。它是脊椎动物中高度保守的复合物，主要参与蛋白酶体降解，这对于维持细胞周期、DNA 修复和分化等过程至关重要。在本研究中，我们使用生物信息学和计算机模拟分析结合体内 LPS 暴露策略、下一代测序（NGS）和 qRT-PCR 来阐明分子和 Mif 细胞因子、Csn 信号成分和 Nf-κB 信号通路的时间动态。对转录组数据中选择的免疫基因进行 qRT-PCR 分析显示，炎症反应呈双相激活。系统发生和 STRING 分析表明，在 LPS 介导的炎症反应中，海鞘中的 Mif-Csn-Nf-kB 轴之间存在进化保守的功能联系，由非编码分子（如 microRNAs (miRNAs)）精细调节。
