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Int J Biol Macromol. 2019 Feb 15;123:157-166. doi: 10.1016/j.ijbiomac.2018.11.066. Epub 2018 Nov 13.

Polysaccharide from Phellinus Igniarius activates TLR4-mediated signaling pathways in macrophages and shows immune adjuvant activity in mice.

Author information

1
School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
2
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
3
Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang, China.
4
Zhejiang Pharmaceutical College, Ningbo 315100, Zhejiang, China.
5
School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. Electronic address: zhj@zcmu.edu.cn.
6
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China. Electronic address: wengcp@163.com.

Abstract

Polysaccharide from Phellinus igniarius (PPI) is known for its immune-regulating effect with low toxicity. Toll like receptor 4 (TLR4) is important in both innate and adaptive immune responses and considered to be a promising target for new immune adjuvants. In this study, PPI was investigated for its effect on activating TLR4 in RAW264.7 and peritoneal macrophages. The adjuvant potential of PPI was evaluated in OVA-immunized mice. The results showed PPI treatment significantly increased the secretion and the mRNA expression of both MyD88 dependent and TRIF dependent cytokines. IRAK-1, a key molecule on the downstream of MyD88, was polyubiquitinated while IRF-3, another key molecule on the downstream of TRIF, was phosphorylated obviously after the treatment of PPI. The phosphorylation of molecules involved in both NF-κB pathway and MAPK pathway were significantly up-regulated after PPI treatment. In addition, the effects of PPI on the macrophages almost completely disappeared after treating the cells with the TLR4 antagonist TAK-242. Further in vivo results showed PPI significantly increased the serum OVA-specific antibody and the OVA-specific spleen cell proliferation. Taken together, PPI can specifically stimulate TLR4 and activate both MyD88 and TRIF pathways. PPI has immune adjuvant activity and may become a new potential immune adjuvant.

KEYWORDS:

Adjuvant; Phellinus Igniarius; Polysaccharide; TLR4

PMID:
30439422
DOI:
10.1016/j.ijbiomac.2018.11.066
[Indexed for MEDLINE]

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