酪蛋白酶解肽谱对树突状细胞成熟的影响
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摘要
酪蛋白经水解制得的多肽是重要的生物活性肽,具有免疫调节能力。本研究分别利用胰蛋白酶及胃蛋白酶的酶解酪蛋白,经乙醇、超滤以及Sephadex G-25两次分离纯化后,制备两种不同的酪蛋白水解多肽。一方面以Balb/c小鼠为实验动物,分别将同一浓度的胰蛋白酶水解的酪蛋白多肽通过口服,腹腔注射和静脉注射给药。利用悬浮液体芯片系统,检测小鼠外周血血清中24种细胞因子的浓度变化,研究胰蛋白酶酪蛋白水解多肽对小鼠细胞因子网络的影响并推测产生的先天免疫应答。结果灌胃组中,大部分细胞因子的水平是升高的,抗炎细胞因子IL-5,IL-9,IL-10,MIP-1α是降低的,说明酪蛋白水解多肽促进发炎细胞因子的合成,具有刺激免疫升高的作用。腹腔注射组与此类似。静脉注射的酪蛋白水解多肽对细胞因子水平的影响与灌胃组、腹腔注射组相比明显不同。因为多肽不经过肠粘膜免疫系统直接进入血液,推测通过激活多种免疫细胞内部不同的信号途径影响了细胞因子的基因表达。另一方面诱导培养C57BL/6雄性小鼠骨髓源的树突状细胞(Dendritic cells),用不同浓度的水解多肽刺激DCs,在48h后进行流式细胞仪检测,鉴定DCs的成熟程度,并将成熟后的DCs与T细胞共孵育96h,CCK-8检测T细胞增殖。结果表明:两种酶水解酪蛋白多肽均能够刺激DCs的成熟,但刺激程度低于阳性对照LPS。而且成熟的DCs能够刺激T细胞增殖,说明DCs具有对这些多肽的抗原递呈能力。其上清液中的细胞因子IL-1α、IL-β、IL-2、IL-6、IL-12的分泌提高, TNF-α、IFN-γ浓度降低,促使幼稚T细胞向Th2极化。说明酪蛋白水解多肽对获得性免疫具有信号传递作用。
The polypeptides derived from casein are important biological active peptides(BAP), which have obvious immunostimulating properties. Polypeptides were separated from tryptic and peptic casein hydrolysates by ethanol sedimentation, ultrafiltration and two rounds of Sephadex G-25 chromatography. First, use Millipore mouse Cytokine kits to test the concentrations of 24 cytokines in serum of mouse, which treated with polypeptides were separated from tryptic casein hydrolysates (TCH) through oral administration, intraperitoneal injection, intravenous injection to study the effects of peptides on the cytokine network and the impacts of innate immune response . The results indicated that, the concentrations of most of cytokines in serum of mouse were grown besides the anti-inflammatory cytokines as IL-5,IL-9,IL-10,MIP-1αwere reduced in the oral administration group; similar to the intraperitoneal injection group. The results of intravenous injection group was significantly different compared with the other two groups, which show that the peptide go to blood directly but not thought mucosal immune system, and activate a variety of different signaling pathways in immunocyte then change the gene expression of cytokine . Second, bone marrow-derived dendritic cells(DCs), which were generated from male C57BL/6 mouse were stimulated by casein-derived polypeptides, and 24 hours later, cells were tested on flow cytometry . The stimulated DCs and T cells were co-cultured 96 hours, and T cells proliferation was assayed using CCK-8 kit .The result show that two kinds of casein-derived polypeptides were able to stimulate DCs to mature, but the stimulation was lower than the LPS which as a positive control .And mature DCs can stimulate T cell proliferation, indicating DCs had the ability to present of the polypeptide. The concentrations of IL-1α, IL-β, IL-2, IL-6, IL-12 in clear supernatant liquid were increased, and the concentration of TNF-α, IFN-γwere decreased, indicating the Th2 polarization of naive T. The result shows that the casein-derived polypeptides have a regulating function on the acquired immune function.
The polypeptides derived from casein are important biological active peptides(BAP), which have obvious immunostimulating properties. Polypeptides were separated from tryptic and peptic casein hydrolysates by ethanol sedimentation, ultrafiltration and two rounds of Sephadex G-25 chromatography. First, use Millipore mouse Cytokine kits to test the concentrations of 24 cytokines in serum of mouse, which treated with polypeptides were separated from tryptic casein hydrolysates (TCH) through oral administration, intraperitoneal injection, intravenous injection to study the effects of peptides on the cytokine network and the impacts of innate immune response . The results indicated that, the concentrations of most of cytokines in serum of mouse were grown besides the anti-inflammatory cytokines as IL-5,IL-9,IL-10,MIP-1αwere reduced in the oral administration group; similar to the intraperitoneal injection group. The results of intravenous injection group was significantly different compared with the other two groups, which show that the peptide go to blood directly but not thought mucosal immune system, and activate a variety of different signaling pathways in immunocyte then change the gene expression of cytokine . Second, bone marrow-derived dendritic cells(DCs), which were generated from male C57BL/6 mouse were stimulated by casein-derived polypeptides, and 24 hours later, cells were tested on flow cytometry . The stimulated DCs and T cells were co-cultured 96 hours, and T cells proliferation was assayed using CCK-8 kit .The result show that two kinds of casein-derived polypeptides were able to stimulate DCs to mature, but the stimulation was lower than the LPS which as a positive control .And mature DCs can stimulate T cell proliferation, indicating DCs had the ability to present of the polypeptide. The concentrations of IL-1α, IL-β, IL-2, IL-6, IL-12 in clear supernatant liquid were increased, and the concentration of TNF-α, IFN-γwere decreased, indicating the Th2 polarization of naive T. The result shows that the casein-derived polypeptides have a regulating function on the acquired immune function.
引文
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