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

[1]	. Cell Mol Neurobiol，2015，35（1）：71?83.
[2]	Tiwari S，Atluri V，Kaushik A，et al. Alzheimer''''s disease：pathogenesis，diagnostics，and therapeutics［J］. Int J Nanomed，2019，14：5541?5554.
[3]	Wyss-Coray T. Inflammation in Alzheimer disease：driving force，bystander or beneficial response ［J］？ Nat Med，2006，12（9）：1005?1015.
[4]	Orre M，Kamphuis W，Osborn LM，et al. Isolation of Glia from Alzheimer''''s mice reveals inflammation and dysfunction［J］. Neurobiol Aging，2014，35（12）：2746?2760.
[5]	Fang YQ，Wang JN，Yao LM，et al. The adhesion and migration of microglia to β-amyloid （Aβ）is decreased with aging and inhibited by Nogo/NgR pathway［J］. J Neuroinflammation，2018，15（1）：210.
[6]	Kushner I. The phenomenon of the acute phase response［J］. Ann N Y Acad Sci，1982，389：39?48.
[7]	Ye RD，Sun L. Emerging functions of serum amyloid A in inflammation［J］. J Leukoc Biol，2015，98（6）：923?929.
[8]	Abuduhalike R，Sun J，Zhao L，et al. Correlation study of venous thromboembolism with SAA，IL-1，and TNF-α levels and gene polymorphisms in Chinese population［J］. J Thorac Dis，2019，11（12）：5527?5534.
[9]	Yu Y，Liu J，Li SQ，et al. Serum amyloid a differentially activates microglia and astrocytes via the PI3K pathway［J］. J Alzheimers Dis，2014，38（1）：133?144.
[10]	Liang JS，Sloane JA，Wells JM，et al. Evidence for local production of acute phase response apolipoprotein serum amyloid A in Alzheimer''''s disease brain［J］. Neurosci Lett，1997，225（2）：73?76.
[11]	Miida T，Yamada T，Seino U，et al. Serum amyloid A （SAA）-induced remodeling of CSF-HDL［J］. Biochim Biophys Acta，2006，1761（4）：424?433.
[12]	Kindy MS，Yu J，Guo JT，et al. Apolipoprotein serum amyloid A in Alzheimer''''s disease［J］. J Alzheimer''''s Dis，1999，1（3）：155?167.
[13]	Guo JT，Yu J，Grass D，et al. Inflammation-dependent cerebral deposition of serum amyloid a protein in a mouse model of amyloidosis［J］. J Neurosci，2002，22（14）：5900?5909.
[14]	Jang S，Jang WY，Choi M，et al. Serum amyloid A1 is involved in amyloid plaque aggregation and memory decline in amyloid beta abundant condition［J］. Transgenic Res，2019，28（5/6）：499?508.
[15]	Zhang M，Sun LH，Yao HB，et al. Effects of PI3K/Akt signaling pathway on serum C-reactive protein，serum amyloid A and cognitive dysfunction in mice with Alzheimer''''s disease［J］. Int J Clin Exp Med 2019，12（12）：13437?13445.
[16]	Su SB，Gong W，Gao JL，et al. A seven-transmembrane，G protein-coupled receptor，FPRL1，mediates the chemotactic activity of serum amyloid A for human phagocytic cells［J］. J Exp Med，1999，189（2）：395?402.
[17]	Badolato R，Wang JM，Murphy WJ，et al. Serum amyloid A is a chemoattractant：induction of migration，adhesion，and tissue infiltration of monocytes and polymorphonuclear leukocytes［J］. J Exp Med，1994，180（1）：203?209.
[18]	Urieli-Shoval S，Linke RP，Matzner Y. Expression and function of serum amyloid A，a major acute-phase protein，in normal and disease states［J］. Curr Opin Hematol，2000，7（1）：64?69.
[19]	Furlaneto CJ，Campa A. A novel function of serum amyloid A：a potent stimulus for the release of tumor necrosis factor-alpha，interleukin-1beta，and interleukin-8 by human blood neutrophil［J］. Biochem Biophys Res Commun，2000，268（2）：405?408.
[20]	De Buck M，Gouwy M，Wang JM，et al. The cytokine-serum amyloid A-chemokine network［J］. Cytokine Growth Factor Rev，2016，30：55?69.
[21]	Huang C，Jacobson K，Schaller MD. MAP kinases and cell migration［J］. J Cell Sci，2004，117（Pt 20）：4619?4628.
[22]	Hauck CR，Sieg DJ，Hsia DA，et al. Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells［J］. Cancer Res，2001，61（19）：7079?7090.
[23]	Kotlyarov A，Yannoni Y，Fritz S，et al. Distinct cellular functions of MK2［J］. Mol Cell Biol，2002，22（13）：4827?4835.
[24]	Jana A，Krett NL，Guzman G，et al. NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway［J］. Oncotarget，2017，8（23）：37377?37393.
[25]	Mou HW，Li ZM，Kong Y，et al. Proinflammatory stimulants promote the expression of a promiscuous G protein-coupled receptor，mFPR2，in microvascular endothelial cells［J］. Inflammation，2012，35（2）：656?664.
[26]	Chiou，Lin CY. Der p2 activates airway smooth muscle cells in a TLR2/MyD88-dependent manner to induce an inflammatory response［J］. J Cell Physiol，2009，220（2）：311?318.
[27]	Liu J，Wang D，Li SQ，et al. Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A［J］. J Neuroinflammation，2016，13：28.

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