Mechanism of Innate Immune Response Induced by Albizia julibrissin Saponin Active Fraction Using C2C12 Myoblasts.
Mechanism of Innate Immune Response Induced by Albizia julibrissin Saponin Active Fraction Using C2C12 Myoblasts.
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DOI：
10.3390/vaccines11101576
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发表时间：
2023-10-10
期刊：
影响因子：
7.8
通讯作者：
Sun H
中科院分区：
文献类型：
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作者：
Du J;Meng X;Ni T;Xiong B;Han Z;Zhu Y;Tu J;Sun H
合欢皂苷活性组分（AJSAF）具有Th 1/Th 2和Tc 1/Tc 2双重增强活性，是一种很有前景的佐剂。其佐剂活性先前已被证明严格依赖于其与抗原的空间共定位，突出了局部先天免疫在其机制中的作用。然而，其潜在目标和途径仍不清楚。在这里，它的先天性免疫反应的细胞内分子机制进行了探索，使用小鼠C2 C12成肌细胞的整合分析，在体内和体外转录组结合实验验证。AJSAF引起对C2 C12细胞的暂时性细胞毒性和炎症。基因集富集分析表明，AJSAF通过激活第二信使-MAPK-CREB途径，在体外和体内调节相似的细胞死亡和炎症反应相关基因。AJSAF可显著提高C2 C12细胞内Ca ~（2+）、cAMP和活性氧水平，促进MAPK和CREB磷酸化。此外，Ca 2+螯合剂、CREB抑制剂和MAPK抑制剂显著阻断AJSAF处理的C2 C12细胞中IL-6、CXCL 1和COX 2的上调。总之，这些结果表明AJSAF通过Ca 2 +-MAPK-CREB途径诱导先天免疫。本研究有助于深入了解皂苷佐剂的分子机制。
Albizia julibrissin saponin active fraction (AJSAF), is a prospective adjuvant with dual Th1/Th2 and Tc1/Tc2 potentiating activity. Its adjuvant activity has previously been proven to be strictly dependent on its spatial co-localization with antigens, highlighting the role of local innate immunity in its mechanisms. However, its potential targets and pathways remain unclear. Here, its intracellular molecular mechanisms of innate immune response were explored using mouse C2C12 myoblast by integrative analysis of the in vivo and in vitro transcriptome in combination with experimental validations. AJSAF elicited a temporary cytotoxicity and inflammation towards C2C12 cells. Gene set enrichment analysis demonstrated that AJSAF regulated similar cell death- and inflammatory response-related genes in vitro and in vivo through activating second messenger–MAPK–CREB pathways. AJSAF markedly enhanced the Ca2+, cAMP, and reactive oxygen species levels and accelerated MAPK and CREB phosphorylation in C2C12 cells. Furthermore, Ca2+ chelator, CREB inhibitor, and MAPK inhibitors dramatically blocked the up-regulation of IL-6, CXCL1, and COX2 in AJSAF-treated C2C12 cells. Collectively, these results demonstrated that AJSAF induced innate immunity via Ca2+–MAPK–CREB pathways. This study is beneficial for insights into the molecular mechanisms of saponin adjuvants.
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DOI：
10.1073/pnas.1319784110
发表时间：
2013-12-24
影响因子：
11.1
作者：
Vono, Maria;Taccone, Marianna;Seubert, Anja
通讯作者：
Seubert, Anja
影响因子：
5.5
作者：
Gavala, Monica L.;Pfeiffer, Zachary A.;Bertics, Paul J.
通讯作者：
Bertics, Paul J.
影响因子：
5.8
作者：
Palmai-Pallag, Timea;Bachrati, Csanad Z.
通讯作者：
Bachrati, Csanad Z.
天然和合成皂苷作为疫苗佐剂。
影响因子：
7.8
作者：
Wang P
通讯作者：
Wang P
疫苗佐剂可以接合交叉呈递途径。
影响因子：
7.3
作者：
通讯作者：
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