Polysaccharide of Atractylodes macrocephala Koidz (PAMK) Alleviates Cyclophosphamide-induced Immunosuppression in Mice by Upregulating CD28/IP3R/PLCγ-1/AP-1/NFAT Signal Pathway.

Xuelian Xiang,Danning Xu,Feiyue Chen,Long Qian,Yifei Wang,Wanyan Li,Yunbo Tian,Nan Cao,Yunmao Huang

doi:10.3389/fphar.2020.529657

Abstract

The polysaccharide of Atractylodes macrocephala Koidz (PAMK) is recognized as an immune enhancer, with anti-cancer, anti-tumour, lymphocyte-activating and lymphocytes proliferation-inducing effects. For investigating the mechanism that PAMK alleviates the decline in T cell activation induced by CTX, 24 6-week-old BALB/c female mice were randomly divided into four groups (C, PAMK, CTX, PAMK + CTX). The spleen index, splenocytes morphology and death, cytokine concentration, T cell activating factors (CD25, CD69, CD71), mRNA expression levels related to the CD28 signal pathway were detected. Furthermore, the lymphocytes of mice was isolated and cultured, and then the Th1/Th2 ratio, activating factors, mRNA levels related to the CD28 signal pathway were detected. The results showed that PAMK significantly improved the spleen index, alleviated abnormal splenocytes morphology and death, maintained the balance of Th1/Th2 cells, increased the levels of IL-2, IL-6, TNF-α, and IFN-γ, and increased the mRNA levels of CD28, PLCγ-1, IP3R, NFAT, and AP-1. In conclusion, PAMK increased cytokines levels and alleviated the decline in activation level of lymphocytes induced by CTX through CD28/IP3R/PLCγ-1/AP-1/NFAT signal pathway.

Highlights

The polysaccharide of Atractylodes macrocephala Koidz (PAMK), the main active ingredient of Atractylodes macrocephala, has been confirmed to possess anti-oxidative, anti-inflammatory, antitumour, and anti-cancer properties, to relieve heat stress and to improve immunity (Xu and Tian, 2015; Guo et al, 2019)
All the results showed that PAMK could alleviate the decline in the mRNA expression levels of CD28, IP3R, PLCγ-1, NFAT, and AP-1 induced by siCD28
The results indicated that CTX could lead to spleen characterized by lymphocytes having an incomplete morphology, a loose and irregular arrangement, a large number of macrophages, fibrous tissue hyperplasia, increased apoptotic cells and apoptotic bodies, which indicated that the mouse immunosuppressive model was successful constructed

Summary

Introduction

The polysaccharide of Atractylodes macrocephala Koidz (PAMK), the main active ingredient of Atractylodes macrocephala, has been confirmed to possess anti-oxidative, anti-inflammatory, antitumour, and anti-cancer properties, to relieve heat stress and to improve immunity (Xu and Tian, 2015; Guo et al, 2019). PAMK can significantly improve index of spleen and thymus and spleen lymphocytes proliferation, promote T lymphocytes to enter S and G2/M phases, and increase T/B cell proportions, NK cytotoxicity, cytokine levels (IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ), and serum specific immunoglobulin G (IgG) titers, thereby improving immune function (Li. Polysaccharide of Atractylodes Macrocephala Koidz (PAMK) Cyclophosphamide CD28 et al, 2009; Guo et al, 2012b; Liu et al, 2015; Xu et al, 2019). Xu et al found that PAMK alleviated heat stress by decreasing levels of TNF-α, IFN-γ, IL-4, heat shock protein 60 (HSP60), and heat shock protein 70 (HSP70) in chicken (Xu and Tian, 2015). Exploring the signaling pathway that PAMK alleviates the immunosuppression in mice induced by cyclophosphamide (CTX) would be exciting research interest

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Conclusion