Effect of serum amyloid A on microglial migration and its mechanism

LIN Aihua; LIU Jin; CHEN Yanqing; ZHANG Yan; YU Yang

doi:10.11665/j.issn.1000-5048.20200511

Journal of China Pharmaceutical University > 2020 > 51(5): 591-598. > DOI: 10.11665/j.issn.1000-5048.20200511

LIN Aihua, LIU Jin, CHEN Yanqing, ZHANG Yan, YU Yang. Effect of serum amyloid A on microglial migration and its mechanism[J]. Journal of China Pharmaceutical University, 2020, 51(5): 591-598. DOI: 10.11665/j.issn.1000-5048.20200511

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Effect of serum amyloid A on microglial migration and its mechanism

Funds: This study was supported by the National Natural Science Foundation of China (No. 81870835 and No. 81571027)

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Received Date: April 06, 2020
Revised Date: June 15, 2020

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Abstract

Abstract

To investigate the effect of serum amyloid A (SAA) on microglial migration and its mechanism,the migration ability of SAA-induced primary microglia and murine N9 microglia,and the effect of formyl peptide receptor 2 (FPR2) antagonist and TLR2 neutralizing antibody on SAA-induced migration of N9 microglia were all examined by Transwell assay. The expression changes of FPR2 and Toll-like receptor 2 (TLR2) in N9 microglia after SAA stimulation were detected by real-time PCR. The effect of SAA on the expression of downstream signaling pathway kinases in N9 microglia was detected by Western blot. The effect of signaling pathway inhibitors on SAA-induced N9 microglial migration was examined by Transwell assay. The results showed that SAA promoted the migration of primary microglia and N9 microglia in a concentration-dependent manner. FPR2 antagonist and TLR2 neutralizing antibody inhibited SAA-induced N9 cell migration. SAA promoted increased mRNA transcript levels of FPR2 and TLR2 in N9 microglia,and stimulated the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) signaling pathways in N9 microglia,as shown by increased extracellular regulated protein kinase (ERK),p38 and c-Jun N-terminal kinase (JNK) phosphorylation levels and decreased IκBα expression levels. Inhibitors of p38,JNK,and NF-κB signaling pathways inhibited SAA-induced migration of N9 microglia. The difference between the groups was statistically significant (P<0.05). These results indicate that SAA activates downstream p38,JNK,and NF-κB signaling pathways by acting on FPR2 and TLR2,thereby inducing microglia migration.
- serum amyloid A,
- microglia,
- migration,
- receptor,
- signaling pathway

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References (27)

References

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