Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, A.P. 510-3, Cuernavaca 62250, Mexico.
Laboratorio de Investigación Traslacional and Laboratorio Nacional de Citometría de Flujo-UACH, Universidad Autónoma de Chihuahua, Circuito Universitario, Campus II, Chihuahua 31109, Mexico.
Molecules. 2021 Sep 14;26(18):5573. doi: 10.3390/molecules26185573.
In vitro assays of phagocytic activity showed that the peptide Pin2[G] stimulates phagocytosis in BMDM cells from 0.15 to 1.25 μg/mL, and in RAW 264.7 cells at 0.31 μg/mL. In the same way, the peptide FA1 induced phagocytosis in BMDM cells from 1.17 to 4.69 μg/mL and in RAW 264.7 cells at 150 μg/mL. Cytokine profiles of uninfected RAW 264.7 showed that Pin2[G] increased liberation TNF (from 1.25 to 10 μg/mL) and MCP-1 (10 μg/mL), and FA1 also increased the release of TNF (from 18.75 to 75 μg/mL) but did not increase the liberation of MCP-1. In RAW 264.7 macrophages infected with serovar Typhimurium, the expression of TNF increases with Pin2[G] (1.25-10 μg/mL) or FA1 (18.75-75 μg/mL). In these cells, FA1 also increases the expression of IL-12p70, IL-10 and IFN-γ when applied at concentrations of 37.5, 75 and 150 μg/mL, respectively. On the other hand, stimulation with 1.25 and 10 μg/mL of Pin2[G] promotes the expression of MCP-1 and IL-12p70, respectively. Finally, peptides treatment did not resolve murine gastric infection, but improves their physical condition. Cytokine profiles showed that FA1 reduces IFN-γ and MCP-1 but increases IL-10, while Pin2[G] reduces IFN-γ but increases the liberation of IL-6 and IL-12p70. This data suggests a promising activity of FA1 and Pin2[G] as immunomodulators of gastric infections in Typhimurium.
体外吞噬活性测定表明,肽 Pin2[G]在 0.15 至 1.25μg/mL 时刺激 BMDM 细胞吞噬作用,在 0.31μg/mL 时刺激 RAW 264.7 细胞吞噬作用。同样,肽 FA1 在 1.17 至 4.69μg/mL 时刺激 BMDM 细胞吞噬作用,在 150μg/mL 时刺激 RAW 264.7 细胞吞噬作用。未感染的 RAW 264.7 细胞的细胞因子谱表明,Pin2[G]增加 TNF(从 1.25 至 10μg/mL)和 MCP-1(10μg/mL)的释放,FA1 也增加 TNF 的释放(从 18.75 至 75μg/mL),但不增加 MCP-1 的释放。在感染血清型鼠伤寒沙门氏菌的 RAW 264.7 巨噬细胞中,Pin2[G](1.25-10μg/mL)或 FA1(18.75-75μg/mL)的表达增加。在这些细胞中,FA1 还分别在浓度为 37.5、75 和 150μg/mL 时增加 IL-12p70、IL-10 和 IFN-γ 的表达。另一方面,用 1.25 和 10μg/mL 的 Pin2[G]刺激分别促进 MCP-1 和 IL-12p70 的表达。最后,肽处理不能解决小鼠胃感染,但改善其身体状况。细胞因子谱表明,FA1 降低 IFN-γ 和 MCP-1,但增加 IL-10,而 Pin2[G]降低 IFN-γ,但增加 IL-6 和 IL-12p70 的释放。这些数据表明,FA1 和 Pin2[G]作为鼠伤寒沙门氏菌胃感染的免疫调节剂具有很大的应用前景。