title: Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo.
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.
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Clinical Medicine, Xinjiang Medical University, Xinjiang, China.
authors.forename: Zijing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Long
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D053594:Myeloid Differentiation Factor 88; D010936:Plant Extracts; D011134:Polysaccharides; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide