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MHC II-PIK/Akt/mTOR 信号通路调控大豆球蛋白诱导的杂交石斑鱼肠道免疫反应:丁酸钠的保护作用。

MHC II-PIK/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate.

机构信息

Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, China.

Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, China.

出版信息

Front Immunol. 2021 Jan 18;11:615980. doi: 10.3389/fimmu.2020.615980. eCollection 2020.

DOI:10.3389/fimmu.2020.615980
PMID:33537033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7849651/
Abstract

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PIK/T-PIK, P-Akt/T-Akt, and P-mTOR/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PIK and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PIK/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.

摘要

大豆球蛋白(11S)参与免疫调节。作为一种添加剂,丁酸钠(SB)可以缓解 11S 引起的炎症。为了进一步研究其机制,我们采用了 50%鱼粉饲料作为对照组(FM 组),实验组分别为 FM 组基础饲料添加 2%大豆球蛋白(GL 组)、8%大豆球蛋白(GH 组)和 8%大豆球蛋白+0.13%丁酸钠(GH-SB 组)。GL 组的特定生长率(SGR)、饲料利用率和远端肠(DI)II 型粘液细胞密度均升高。GL 组血清中 IFN-γ显著上调,GH 组 IgG 和 IL-1β上调。GH-SB 组 IgG、IL-1β和 TNF-α水平明显低于 GH 组。DI 中 GL、GH 和 GH-SB 组 mTOR C1、mTOR C2 和 Deptor 的 mRNA 水平均高于 FM 组,而 GH 组 mTOR C1 和 Deptor 的 mRNA 水平高于 GL 和 GH-SB 组。GH 组 4E-BP1、RICTOR、PRR5、MHC II 和 CD4 上调。GL 和 GH-SB 组的 TSC1、mLST8 和 NFY mRNA 水平均高于 FM 和 GH 组。Western blot 显示 GH 组 P-PIK/T-PIK、P-Akt/T-Akt 和 P-mTOR/T-mTOR 上调。结果表明,低剂量 11S 通过分泌 IFN-γ可改善血清免疫功能。高剂量 11S 过度表达 IgG 和 IL-1β 是降低血清免疫功能的原因,补充 SB 可以抑制这种过度表达。低剂量 11S 可通过 mTOR C1 阻断 PIK 和 mTOR C2 的关系,通过 mTOR C1 抑制 4E-BP1 的表达。高剂量 11S 通过 mTOR C1 上调 4E-BP2,加重肠道炎症。SB 可通过阻断 PIK/mTOR C2 和抑制 4E-BP2 来缓解炎症。总之,杂交石斑鱼在不同剂量 11S 下获得了不同的血清和 DI 免疫反应,这些反应最终表现为生长性能。SB 能有效增强血清免疫功能,缓解高剂量 11S 引起的肠道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7849651/4f492b3c8737/fimmu-11-615980-g006.jpg
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