The influence of milk bioactive peptides on skin regenerative potential and rejuvenation is very often limited because of allergic reactions. The current study is aimed at exploring the influence of donkey colostrum and mature milk, human colostrum and mature milk, and β-casein and β-casomorphine-7, on the growth and inflammatory response of the culture of cultured skin fibroblasts exposed to these conditions for twenty-four hours. Their effects on the growth-regulatory kinases and redox-sensitive, proinflammatory transcriptional factor NF-κB were detected by using specific primary antibodies against NF-κB p65, Akt-1, phospho-Akt-1, Erk-1, phospho-Erk-1, JNK, phospho-JNK, phospho-STAT-1, and CD26, while logarithmic integrated fluorescence intensity patterns were recorded by flow cytometry. The downregulation of NF-κB p65 was observed after the exposure of skin fibroblasts to donkey milk and human colostrum, while β-casein and β-casomorphine-7 exerted the opposite effect, which suggests that noncasein bioactive peptides of donkey and human milk may be responsible for anti-inflammatory properties. The exposure to all milk species examined and β-casein leads to the activation of growth-regulatory kinases (Akt1/2/3 kinase, Erk kinase, JNK kinase, and Stat-1 kinase), especially for the p-Erk pathway, which suggests that essential amino acids of casein may be responsible for Erk-induced cell cycle activation and proliferation. The opposite effect was observed when cells were exposed to β-casomorphine-7, which may affect the skin fibroblast survival and their proliferative and regenerative potential. Donkey milk did not significantly change the CD26 antigen expression. In conclusion, our results suggest that among cell signaling molecules, the most sensitive but nonspecific downstream effector is p-Erk kinase, which may point to donkey milk usefulness in wound healing, regenerative, and aesthetic dermatology. The noncasein bioactive peptides of donkey milk may be responsible for the anti-inflammatory property of donkey milk and colostrum, which may indicate the usefulness in the treatment of inflammatory skin diseases.

中文翻译：

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驴和人乳对皮肤成纤维细胞氧化还原敏感和增殖信号通路的再生潜力

由于过敏反应，牛奶生物活性肽对皮肤再生潜力和年轻化的影响通常受到限制。当前的研究旨在探讨驴初乳和成熟牛奶，人初乳和成熟牛奶以及β-酪蛋白和β -Casomorphine-7对暴露于这些条件的培养皮肤成纤维细胞培养物的生长和炎症反应的影响。持续二十四个小时。它们对生长调节激酶和效果氧化还原敏感的，促炎转录因子NF- κ B在通过使用特定的初级抗体对NF-检测κB p65，Akt-1，磷酸化Akt-1，Erk-1，磷酸化Erk-1，JNK，磷酸化JNK，磷酸化STAT-1和CD26，同时通过流式细胞术记录了对数积分荧光强度模式。皮肤成纤维细胞暴露于驴乳和人初乳后观察到NF- κBp65的下调，而β-酪蛋白和β -casomorphine-7发挥相反的作用，这表明驴和人乳的非酪蛋白生物活性肽可能负责抗炎特性。暴露于所有检查过的牛奶种类和β-酪蛋白可激活生长调节激酶（Akt1 / 2/3激酶，Erk激酶，JNK激酶和Stat-1激酶）的激活，特别是对于p-Erk途径而言，这表明酪蛋白的必需氨基酸可能是负责Erk诱导的细胞周期活化和增殖。当细胞暴露于β时观察到相反的效果-casomorphine-7，可能会影响皮肤成纤维细胞的存活及其增殖和再生潜力。驴乳没有显着改变CD26抗原的表达。总之，我们的结果表明，在细胞信号分子中，最敏感但非特异性的下游效应子是p-Erk激酶，这可能表明驴乳在伤口愈合，再生和美学皮肤病学方面的用途。驴乳的非酪蛋白生物活性肽可能负责驴乳和初乳的抗炎特性，这可能表明其在治疗炎症性皮肤病中的有用性。