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卵黄天然卵类球蛋白多肽复合物激活巨噬细胞的新机制。

A Novel Mechanism of Macrophage Activation by the Natural Yolkin Polypeptide Complex from Egg Yolk.

机构信息

Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Str., 53-114 Wrocław, Poland.

出版信息

Int J Mol Sci. 2022 Mar 14;23(6):3125. doi: 10.3390/ijms23063125.

Abstract

Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-β and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.

摘要

衰老是伴随着免疫系统功能不可避免的变化而发生的。它增加了对慢性感染的易感性,对老年人的生活质量产生负面影响。因此,恢复衰老的免疫力已成为一个重要的研究和治疗目标。Yolkin 是一种从鸡蛋蛋黄中分离出来的多肽复合物,具有免疫调节和神经保护活性。鉴于巨噬细胞在病原体识别和抗原呈递中发挥关键作用,我们评估了 yolkin 对 BMDM 细胞系的小鼠骨髓来源巨噬细胞(BMDM)的表型和功能的影响。我们使用流式细胞术确定 yolkin 的生物利用度和 CD80/CD86 的表面共表达,并通过实时 PCR 确定 IL-6、IL-10、TGF-β 和 iNOS mRNA 表达。此外,还确定了 yolkin 对 MAPK 和 PI3K/Akt 激酶调节细胞因子表达的影响。yolkin 刺激细胞会引起细胞形态的显著变化,并增加 CD80/CD86 的表达。使用 ERK、JNK 和 PI3K/Akt 的药物抑制剂,我们表明 yolkin 能够激活这些激酶来控制细胞因子 mRNA 的表达。我们的结果表明 yolkin 是一种很好的巨噬细胞活性调节剂,主要诱导 M1 表型。因此,人们认为 yolkin 具有显著的治疗潜力,代表了开发新型免疫调节药物的有希望的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da9/8949158/74b6e9750753/ijms-23-03125-g001.jpg

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