Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo

作者：Zhou, Lijing; Liu, Zijing; Wang, Zhixue; Yu, Shuang; Long, Tingting; Zhou, Xing; Bao, Yixi^*

来源：Scientific Reports, 2017, 7(1): 44822.

DOI：10.1038/srep44822

• NF-KAPPA-B
• TOLL-LIKE RECEPTORS
• TUMOR-BEARING MICE
• CELL LUNG-CANCER
• INFLAMMATORY RESPONSES
• CYTOKINE EXPRESSION
• ANTITUMOR-ACTIVITY
• RAW264.7 CELLS
• UP-REGULATION
• NITRIC-OXIDE

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-alpha, IL-1 beta 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(+/+) wildtype) tumor-bearing mice, the tumor apoptosis rate, immune organ indexes and the levels of TNF-alpha, IL-1 beta and IL-6 in blood increased and the tumor weight decreased 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)-Myd88(m1.1Defr)/J (MyD88-deficient) tumorbearing 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-kappa B and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-kappa 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.

• 出版日期2017-3-17
• 单位重庆医科大学; 新疆医科大学