<br>卵转铁蛋白通过 TLR4 介导的信号转导途径在 RAW264.7 细胞中发挥双向免疫调节活性,Food Science & Nutrition

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卵转铁蛋白通过 TLR4 介导的信号转导途径在 RAW264.7 细胞中发挥双向免疫调节活性
Food Science & Nutrition ( IF 3.5 ) Pub Date : 2021-09-08 , DOI: 10.1002/fsn3.2569
Zhiying Ru ₁ , Mingsheng Xu ₁ , Gaoxiang Zhu ₁ , Yonggang Tu ₁ , Yan Jiang ₁ , Huaying Du ₁

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本研究以脂多糖（LPS）为体外模型，利用RAW264.7探讨卵转铁蛋白（OVT）的免疫调节功能。结果表明，单独使用OVT（200μg/ml）培养的RAW264.7不仅增强了吞噬细胞的吞噬活性和炎症因子的产生和表达，而且OVT还显着促进了Toll样受体4（TLR4）基因的表达。 OVT (50 μg/ml)显着抑制LPS刺激的RAW264.7炎症因子的分泌和表达，但CD14和TLR4基因表达无明显影响。用 TLR4 抑制剂预处理的 OVT 诱导的巨噬细胞分泌的炎症细胞因子和 NO 下调。我们通过免疫荧光和蛋白质印迹进一步验证了OVT对炎症信号通路相关蛋白的影响，OVT显着促进了MyD88、TLR4以及IκBα和p65的磷酸化，但对IRF3的磷酸化没有显着影响。 OVT促进RAW264.7中ERK和p38的磷酸化，并抑制LPS介导的炎症中MAPK的磷酸化表达。这些结果表明OVT通过TLR4介导的NF-κB/MAPK信号通路具有双向免疫调节功能，即低浓度时表现出抗炎作用，高浓度时表现出免疫增强活性。为OVT的开发利用提供了理论依据。

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Ovotransferrin exerts bidirectional immunomodulatory activities via TLR4-mediated signal transduction pathways in RAW264.7 cells

The immune regulation function of ovotransferrin (OVT) explored using the RAW264.7 was induced by lipopolysaccharide (LPS) as vitro model in this study. The results showed that RAW264.7 cultured with OVT (200 μg/ml) alone not only enhanced the phagocytic activity and the production and expression of inflammatory factors, but also expression of toll-like receptor 4 (TLR4) gene was significantly promoted by OVT. OVT (50 μg/ml) significantly inhibited the secretion and expression of inflammatory factors in LPS-stimulated RAW264.7, but CD14 and TLR4 genes expressions were no obvious effects. Inflammatory cytokines and NO secreted by OVT-induced macrophages pretreated with inhibitors of TLR4 were down-regulated. We further verified the effects of OVT on inflammatory signaling pathway-related proteins through immunofluorescence and western blotting, MyD88, TLR4 and the phosphorylation of IκBα and p65 were significantly promoted by OVT, but there was no significant effects on the phosphorylation of IRF3. OVT promoted the phosphorylation of ERK and p38 in RAW264.7 and inhibited the phosphorylated expression of MAPK in LPS-mediated inflammation. These results indicated that OVT had the bidirectional immunoregulatory function through TLR4-mediated NF-κB/MAPK signaling pathway, that is, anti-inflammatory effect of low concentration and immune-enhancing activity of high concentration were showed. That provides a theoretical utilization for the development and utilization of OVT.

更新日期：2021-11-03

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