S100A9 activates NF-κB to promote TLR7 expression and inflammatory cytokine release in microglia
10.16557/j.cnki.1000-7547.2023.06.002
- VernacularTitle:S100A9激活NF-κB促进小胶质细胞TLR7表达和炎症因子释放
- Author:
Qiao BAI
1
;
Xin ZHOU
;
Xiaoyin ZHANG
;
Shanshan ZHAO
;
Li CHEN
;
Yonggang LIU
Author Information
1. 重庆医科大学基础医学院干细胞与组织工程研究室,重庆 400016
- Keywords:
Sl00 calcium-binding protein A9(S100A9);
microglia;
toll-like receptor 7(TLR7);
tumor necrosis factor alpha(TNF-α);
interleukin 6(IL-6)
- From:
Chinese Journal of Neuroanatomy
2023;39(6):624-632
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of S100 calcium-binding protein A9(S100A9)activation of nuclear factor kappa-B(NF-κB)on the upregulation of toll-like receptor 7(TLR7)expression and the release of inflammatory factors in microglia,as well as its underlying mechanism.Methods:The viability of BV2 microglia was assessed using CCK-8 kit.Transcriptome sequencing was employed to compare differential genes(DEGs)and identify target genes from the pool of differentially expressed genes.This analysis was complemented by GO analysis,KEGG enrichment analysis and the STRING database.The expression of TLR7 mRNA was verified by real time RT-PCR.The expressions of CD68 and CD206 were detected using immunofluorescence.The expressions of CD68,CD206,TLR7,p65,and p-p65 were detected using Western Blot.The level of interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α)were verified by ELISA.Results:Moderate concentrations of S100A9 had no inhibitory effect on microglial viability.Compared to the control group,the experimental group showed a significant increase in the expression level of CD68 pro-tein,while the CD206 protein was decreased.This suggests that S100A9 promotes the activation of BV2 microglia into pro-inflammatory types.TAK-242,an inhibitor of toll-like receptor 4(TLR4),significantly inhibited the expression levels of TNF-α and IL-6 after S100A9 stimulated BV2 cells.Activation of the TLR4/NF-κB pathway promoted the ex-pression of TLR7 protein.Conclusion:The moderate concentration of S100A9 can promote the polarization of microglia towards a proinflammatory direction.It also promotes the expression of TLR7 and the release of various inflammatory factors,including TNF-α and IL-6,through the activation of the TLR4/NF-κB pathway.This activation has an obvious proinflammatory effect.
