Servicio de Aparato Digestivo. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM, CEI UAM+CSIC), Madrid, Spain.
Mol Nutr Food Res. 2021 Jun;65(12):e2001034. doi: 10.1002/mnfr.202001034. Epub 2021 May 13.
Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa.
Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1β, TNF-α, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGFβ, while it also downregulates the expression of iNOS and subunit p65 from NF-κB. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFNγ, and IL-8 expression, and inducing IL-10 and TGFβ expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry.
We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.
Lunasin 是一种具有多种有益特性的大豆生物活性肽,可预防慢性疾病。然而,其在人体原代肠细胞中的作用尚不清楚。因此,本研究旨在表征 Lunasin 在人体肠黏膜中的体外生物学活性。
从健康对照者中获得的人肠活检标本,通过 HPLC-MS/MS 分析,在有/无脂多糖 (LPS) 的情况下,用 Lunasin 进行体外培养。Lunasin 在活检培养过程中保持稳定。Lunasin 在人体黏膜中具有生物活性,因为它可以诱导 IL-1β、TNF-α、IL-17A、CCL2 和 PGE2/COX-2 基因表达,并增加免疫调节因子 IL-10 和 TGFβ 的表达,同时下调 NF-κB 的 iNOS 和亚基 p65 的表达。事实上,Lunasin 还可以阻断 LPS 诱导的促炎反应,下调 IL-17A、IFNγ 和 IL-8 的表达,并诱导 IL-10 和 TGFβ 的表达。这些结果在细胞无培养基上清液中也通过多重免疫分析得到了验证。此外,Lunasin 通过流式细胞术进一步诱导人肠常规树突状细胞和巨噬细胞亚群的调节表型和功能。
我们已经将 Lunasin 鉴定为一种具有免疫调节潜力的肽,可能预防人类胃肠道的免疫和炎症介导的疾病。