Astragalus Polysaccharides Exerts Immunomodulatory Effects via TLR4-mediated MyD88-dependent Signaling Pathway in Vitro and in Vivo

Sci Rep. 2017 Mar 17;7:44822. doi: 10.1038/srep44822.

Abstract

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-α, IL-1β 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 apoptosis rate, immune organ indexes and the levels of TNF-α, IL-1β 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)-Myd88m1.1Defr/J (MyD88-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-κB and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-κB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astragalus Plant / chemistry*
  • Cytokines / metabolism
  • Female
  • Gene Expression
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nitric Oxide / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • Immunologic Factors
  • Myeloid Differentiation Factor 88
  • Plant Extracts
  • Polysaccharides
  • Toll-Like Receptor 4
  • Nitric Oxide