A Study On Immunomodulatory Mechanism Of Astragalus Polysaccharides Mediated By TLR4-mediated MyD88 Dependent Signaling Pathway

Astragalus polysaccharides(APS),which is widely used as a remedy to promote immunity of breast cancer patients,can enhance immune responses and exert anti-tumor effects.In this study,we investigated the effects and mechanisms of APS on macrophage RAW 264.7 and EAC tumor-bearing mice.Griess reaction and ELISA assays revealed that the concentrations of nitric oxide,TNF-?,IL-1? and IL-6 were increased by APS.However,this effect was diminished in the presence of TAK-242(TLR4 inhibitor)or ST-2825(MyD88 inhibitor).In C57BL/10J(TLR4+/+wild-type)and C57BL/6J(MyD88+/+wild-type)tumor-bearing mice,the tumor weight,apoptosis rate,immune organ indexes and the levels of TNF-?,IL-1? and IL-6 in blood were increased by oral administration of APS for 25 days.APS had no obvious effects on IL-12p70.However,these effects were not significant in C57BL/10ScNJ(TLR4-deficient)and C57BL/B6.129P2(SJL)-Myd88m1.1Defr/J(My D88-deficient)tumor-bearing mice.qRT-PCR and Western blot indicated that APS stimulated the key nodes in the TLR4-MyD88 dependent signaling pathway,including TLR4,MyD88,TRAF-6,NF-?B and AP-1,both in vitro and in vivo.However,TRAM was an exception.Moreover,TRAF-6 and NF-?B were not triggered by APS in gene-deficient tumor-bearing mice.Therefore,APS may modulate immunity of host organism through activation of TLR4-mediated MyD88-dependent signaling pathway.