The secretion of sIgA and dendritic cells activation in the intestinal of cyclophosphamide-induced immunosuppressed mice are regulated by Alhagi honey polysaccharides

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.

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