Fundamental and Translational Immunology Group, Dublin City University, Dublin 9, Ireland.
Nutrients. 2019 Jul 23;11(7):1688. doi: 10.3390/nu11071688.
Immunomodulatory nutraceuticals have garnered special attention due to their therapeutic potential for the amelioration of many chronic inflammatory conditions. Macrophages are key players in the induction, propagation and resolution of inflammation, actively contributing to the pathogenesis and resolution of inflammatory disorders. As such, this study aimed to investigate the possible therapeutic effects bovine casein derived nutraceuticals exert on macrophage immunological function. Initial studies demonstrated that sodium caseinate induced a M2-like macrophage phenotype that was attributed to the kappa-casein subunit. Kappa-casein primed macrophages acquired a M2-like phenotype that expressed CD206, CD54, OX40L, CD40 on the cell surface and gene expression of Arg-1, RELM-α and YM1, archetypical M2 markers. Macrophages stimulated with kappa-casein secreted significantly reduced TNF-α and IL-10 in response to TLR stimulation through a mechanism that targeted the nuclear factor-κB signal transduction pathway. Macrophage proteolytic processing of kappa-casein was required to elicit these suppressive effects, indicating that a fragment other than C-terminal fragment, glycomacropeptide, induced these modulatory effects. Kappa-casein treated macrophages also impaired T-cell responses. Given the powerful immuno-modulatory effects exhibited by kappa-casein and our understanding of immunopathology associated with inflammatory diseases, this fragment has the potential as an oral nutraceutical and therefore warrants further investigation.
免疫调节营养保健品因其在改善许多慢性炎症性疾病方面的治疗潜力而受到特别关注。巨噬细胞是诱导、传播和缓解炎症的关键参与者，积极参与炎症性疾病的发病机制和缓解。因此，本研究旨在探讨牛酪蛋白衍生营养保健品对巨噬细胞免疫功能的可能治疗作用。最初的研究表明，酪蛋白酸钠诱导出一种 M2 样巨噬细胞表型，这归因于 κ-酪蛋白亚基。κ-酪蛋白引发的巨噬细胞获得了 M2 样表型，在细胞表面表达 CD206、CD54、OX40L、CD40，并表达 Arg-1、RELM-α 和 YM1 等典型的 M2 标志物。通过靶向核因子-κB 信号转导途径的机制，κ-酪蛋白刺激的巨噬细胞分泌的 TNF-α 和 IL-10 显著减少，对 TLR 刺激的反应。需要巨噬细胞对 κ-酪蛋白的蛋白水解处理来产生这些抑制作用，表明除了 C 端片段糖巨肽外，其他片段诱导了这些调节作用。κ-酪蛋白处理的巨噬细胞还损害了 T 细胞反应。鉴于 κ-酪蛋白表现出强大的免疫调节作用，以及我们对与炎症性疾病相关的免疫病理学的理解，该片段有可能作为口服营养保健品，因此值得进一步研究。
