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The secretion of sIgA and dendritic cells activation in the intestinal of cyclophosphamide-induced immunosuppressed mice are regulated by Alhagi honey polysaccharides
Phytomedicine ( IF 6.7 ) Pub Date : 2022-06-01 , DOI: 10.1016/j.phymed.2022.154232
Gaofeng Cai 1 , Yang Yang 1 , Pengfei Gu 1 , Kui Li 1 , Wusiman Adelijiang 2 , Tianyu Zhu 1 , Zhenguang Liu 1 , Deyun Wang 1
Affiliation  

Background

It remains a huge challenge to recover the intestine immune function for the treatment of intestinal mucosal damage from chemotherapy with cyclophosphamide (CY). Alhagi honey polysaccharide (AH) has immunomodulation pharmacological activity, but the effect and mechanism on the intestinal immune system of CY-mice remain unclear.

Purpose

In this experiment, the immunomodulatory activity of AH on intestinal immune in CY-mice and its mechanism of regulating the intestinal immune system was investigated.

Study design and methods

The experiment studied the immunomodulatory activity of AH on the intestinal immune system and its mechanism for the first time from in vitro and in vivo experiments. We investigated the immunomodulatory effects of AH on Caco-2 and dendritic cells (DCs) in vitro by using western blot (WB), flow cytometry, quantitative real-time PCR (qPCR), and ELISA methods. In vivo experiment, the immunosuppressive mouse model was established through being given intraperitoneal injection with CY (80 mg/kg) for 3 days. Then, mice oral administration of 800 mg/kg AH and 40 mg/kg levamisole hydrochloride for a week. Immunofluorescence, flow cytometry, ELISA, qPCR and WB were applied to examine the immunomodulatory activity of AH on the intestinal immune function of CY-mice, as well as the function of AH on the concentration of SCFAs in cecum by Gas chromatographic analysis.

Results

In vitro experiments, AH could significantly stimulate the expression of pIgR protein in Caco-2. It could also induce the DCs maturation and release the cytokines to regulate the immune response. In vivo experiments, AH could remarkably stimulate the DCs maturation and secrete more CCL20 to recruit DCs, then induce the T (CD4+ and CD8+) and B cells proliferation and activation. Moreover, it could further induce T helper cells to differentiate and secrete cytokines to enhance the secretion of sIgA. Furthermore, it also directly activated DCs and released cytokines to increase the content of pIgR, J-chain, and IgA+ cells in intestine, thereby enhancing the secretion of sIgA to protect the intestine. In addition, AH could obviously strengthen the SCFAs production in cecum to regulate the intestinal immune dysfunction induced by CY.

Conclusion

In summary, oral administrated AH exhibits great benefits for treating CY-induced intestinal immunosuppression, and the mechanism of action mainly involves sIgA, DCs, SCFAs.



中文翻译:

Alhagi 蜂蜜多糖调控环磷酰胺诱导免疫抑制小鼠肠道 sIgA 分泌和树突状细胞活化

背景

恢复肠道免疫功能以治疗环磷酰胺(CY)化疗引起的肠粘膜损伤仍然是一个巨大的挑战。Alhagi蜂蜜多糖(AH)具有免疫调节药理活性,但对CY-小鼠肠道免疫系统的作用和机制尚不清楚。

目的

本实验研究了AH对CY-小鼠肠道免疫的免疫调节活性及其调节肠道免疫系统的机制。

研究设计和方法

本实验首次从体外体内实验研究了AH对肠道免疫系统的免疫调节活性及其作用机制。我们通过使用蛋白质印迹 (WB)、流式细胞术、定量实时 PCR (qPCR) 和 ELISA 方法在体外研究了 AH 对 Caco-2 和树突状细胞 (DC) 的免疫调节作用。体内实验中,腹腔注射CY(80 mg/kg)3天,建立免疫抑制小鼠模型。然后,小鼠口服 800 mg/kg AH 和 40 mg/kg 盐酸左旋咪唑一周。应用免疫荧光、流式细胞术、ELISA、qPCR和WB等方法检测AH对CY-小鼠肠道免疫功能的免疫调节作用,气相色谱分析AH对盲肠SCFAs浓度的影响。

结果

在体外实验中,AH可以显着刺激Caco-2中pIgR蛋白的表达。它还可以诱导 DCs 成熟并释放细胞因子来调节免疫反应。在体内实验中,AH可以显着刺激DCs成熟并分泌更多的CCL20来募集DCs,进而诱导T细胞(CD4 +和CD8 +)和B细胞增殖和活化。此外,它还可以进一步诱导T辅助细胞分化并分泌细胞因子,从而增强sIgA的分泌。此外,它还直接激活 DC,释放细胞因子,增加 pIgR、J-chain 和 IgA +的含量细胞,从而增强sIgA的分泌以保护肠道。此外,AH可明显增强盲肠中SCFAs的产生,从而调节CY诱导的肠道免疫功能障碍。

结论

综上所述,口服 AH 对治疗 CY 诱导的肠道免疫抑制有很大的益处,其作用机制主要涉及 sIgA、DCs、SCFAs。

更新日期:2022-06-05
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