Endotoxin-Binding Peptides Derived from Casein Glycomacropeptide Inhibit Lipopolysaccharide-Stimulated Inflammatory Responses via Blockade of NF-κB activation in macrophages.
Endotoxin-Binding Peptides Derived from Casein Glycomacropeptide Inhibit Lipopolysaccharide-Stimulated Inflammatory Responses via Blockade of NF-κB activation in macrophages.
复制标题
酪蛋白糖巨肽衍生的内毒素结合肽通过阻断巨噬细胞中 NF-κ B 的激活来抑制脂多糖刺激的炎症反应
作者：
Cheng X;Gao D;Chen B;Mao X
全身低度炎症和循环脂多糖（LPS）增加导致代谢功能障碍。研究了酪蛋白糖宏肽（GMP）水解物对lps刺激的巨噬细胞炎症反应的抑制作用及其分子机制。结果表明，木瓜蛋白酶对一氧化氮（NO）生成的抑制作用明显高于胃蛋白酶、碱性蛋白酶和胰蛋白酶对NO生成的抑制作用（p < 0.05），且木瓜蛋白酶水解1 h时的抑制作用最强。与天然GMP相比，GHP显著抑制lps诱导的NO生成，且呈剂量依赖性，诱导型一氧化氮合酶（iNOS） mRNA水平降低。GHP阻断toll样受体4 (TLR4)/髓样分化初级反应88 (MyD88)/核因子-κB （NF-κB）信号通路激活，同时下调lps引发肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β基因表达显著上调。此外，GHP不仅可以通过直接与LPS结合来中和LPS，还可以通过抑制LPS与TLR4/MD2复合物的结合来中和LPS，使其成为潜在的LPS抑制剂。综上所述，这些发现表明，在lps刺激的RAW264.7细胞中，GHP负向调节tlr4介导的炎症反应，因此可能具有改善炎症相关问题的潜力。
Systemic low-grade inflammation and increased circulating lipopolysaccharide (LPS) contribute to metabolic dysfunction. The inhibitory effects and underlying molecular mechanisms of casein glycomacropeptide (GMP) hydrolysate on the inflammatory response of LPS-stimulated macrophages were investigated. Results showed that the inhibitory effect of GMP hydrolysates obtained with papain on nitric oxide (NO) production were obviously higher than that of GMP hydrolysates obtained with pepsin, alcalase and trypsin (p < 0.05), and the hydrolysate obtained with papain for 1 h hydrolysis (GHP) exhibited the highest inhibitory effect. Compared with native GMP, GHP markedly inhibited LPS-induced NO production in a dose-dependent manner with decreased mRNA level of inducible nitric oxide synthase (iNOS). GHP blocked toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway activation, accompanied by downregulation of LPS-triggered significant upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β gene expression. Furthermore, GHP could neutralize LPS not only by direct binding to LPS, but also by inhibiting the engagement of LPS with the TLR4/MD2 complex, making it a potential LPS inhibitor. In conclusion, these findings suggest that GHP negatively regulates TLR4-mediated inflammatory response in LPS-stimulated RAW264.7 cells, and therefore may hold potential to ameliorate inflammation-related issues.