Effect of TGF-βactivated kinase-1 inhibitor on bone marrow-derived macrophages activation and its mechanism
10.3969/j.issn.1001-1978.2016.03.012
- VernacularTitle:转化生长因子-β激活激酶1抑制剂对AGEs诱导小鼠骨髓来源巨噬细胞活化作用及机制
- Author:
Xin FU
;
Xingxin XU
;
Yunxia SHAO
;
Shiyao FENG
;
Yuanyuan LI
;
Yonggui WU
- Publication Type:Journal Article
- Keywords:
advanced glycation end products;
TAK1;
MAPK;
NF-κB;
macrophage;
inflammation
- From:
Chinese Pharmacological Bulletin
2016;32(3):355-360,361
- CountryChina
- Language:Chinese
-
Abstract:
Aim We used bone marrow-derived macro-phages ( BMMs ) , to explore the mechanism of macro-phage activation and the effect of TGF-β activated ki-nase-1 ( TAK1 ) inhibitor 5 Z-7-oxozeaenol on it under AGEs conditions. Methods The BMMs were obtained from C57 mice, and purity of BMMs was detected by flow cytometry. Cell viability was tested after treatment with different concentrations of TAK1 inhibitors. Laser confocal microscopy was used to detect macrophage M1 subtype . Flow cytometry was used to analyse the macro-phage activated by AGEs. TNF-α and MCP-1 mRNA levels were evaluated by qRT-PCR. Western blot was used to detect the expression levels of TAK1 signal pathway protein. Results AGEs stimulation could in-crese the activity of M1 macrophages,and 5Z-7-oxoze-aenol could inhibit the differentiation of BMMs. Com-pared with control group, AGEs increased the expres-sion of MCP-1 and TNF-α mRNA(P<0. 01). p-TAK1, TAB1,p-JNK,p-p38MAPK and NF-κBp65 proteins ex-pression also increased significantly ( P <0. 05 ) . After treatment with inhibitor, transcription levels of MCP-1 and TNF-α decreased significantly ( P < 0. 05 , P <0. 01 ) . 5 Z-7-oxozeaenol treatment downregulated the expression of p-TAK1,TAB1,p-JNK,p-p38MAPK and
NF-κBp65 proteins ( P <0. 05 ) . Conclusions AGEs can induce BMMs to M1 phenotypic polarization. 5Z-7-oxozeaenol reduces the expression of inflammatory cyto-kine via inhibiting TAK1/MAPKs, MAPKs/NF-κB pathways.
