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A novel chrysin thiazole derivative polarizes macrophages to an M1 phenotype via targeting TLR4.

Abstract：

:Tumor-associated macrophages (TAMs) are an important cause of tumorigenesis and tumor development. M2 macrophages can promote tumor growth while M1 macrophages kill tumor cells, therefore, polarizing macrophages to achieve a functional M1 phenotype could effectively play its anti-tumor role. In the current study, we synthesized a novel chrysin derivative which is termed as ChR-TD. And we found ChR-TD might be a ligand of TLR4 that polarized the TAMs towards M1 phenotype and played its anti-tumor role. Further study indicated that ChR-TD reprogrammed the macrophages into an M1 phenotype via TLR4 activation. Moreover, ChR-TD activated TLR4/NF-κB signaling pathway and promoted the NF-κB/p65 translocated into the nuclear, leading to the activation of NF-κB and proinflammatory cytokines release. In addition, type I interferon signaling was also activated by ChR-TD, leading to the expressions of IFN-α and IFN-β and its targeted genes NOS2, MCP-1 and IP-10 were significantly increased in macrophages. Importantly, these effects were disturbed in TLR4-/- macrophages, which are constructed by using CRISPR/Cas9 system. And the molecule docking simulation further indicated that ChR-TD could bind to TLR4 and might be a ligand of TLR4. Hence, these findings suggested that ChR-TD might be a ligand of TLR4 and can be used as a potential lead compound for tumors treatment.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Feng X,Yu W,Cao L,Meng F,Cong M

doi

10.1016/j.intimp.2020.106986

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

106986

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(20)31431-4

journal_volume

88

pub_type

杂志文章

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