Effects of adenosine A2A receptor antagonist on lipopolysaccharide induced inflammatory BV-2 microglial cells' morphology and function

doi:10.12092/j.issn.1009-2501.2019.12.010

Abstract

Abstract:

AIM: To investigate the therapeutic effects of adenosine A2A receptor antagonist on experimental autoimmune encephalomyelitis (EAE) and to explore the regulating effects on microglia morphology and function. METHODS: EAE model was induced by MOG35-55 in C57BL/6 mice. Adenosine A2AR antagonists were given by intraperitoneal injection as EAE mice showed neurobehavioral deficits. The treatment lasted ten days until EAE mice reached highest clinical score. ELISA method was used to detect the expression of pro-inflammatory cytokine in central nervous system; immunofluorescence double staining was used to detect M1 cell related markers and M2 cell related markers in microglia. In vitro, activated BV-2 microglia cell line was induced by lipopolysaccharide (LPS) and then was intervened by the A2AR antagonists. Real-time PCR and ELISA method were used to detect the M1 and M2 cells related cytokines. Western Blot method was used to detect the synthesis of M1 and M2 cell related markers. RESULTS:Adenosine A2AR antagonists can effectively ameliorate the EAE-induced neurobehavioral deficits when treated after onset of EAE, and can reduce the secretion of pro-inflammatory cytokine IFN-γ, and M1 cells related iNOS synthesis while increased M2 type cells related ArgI synthesis. Adenosine A2AR antagonists can reduce LPS-induced BV-2 M1 microglial cells related cytokines IL-1β, and had no influence on M2 cells related cytokines and protein. CONCLUSION: Adenosine A2AR antagonists have definite therapeutic effect on EAE mice when treated after the onset of EAE; its underlying mechanism may be involved with shift of phenotype (M1/M2) and changes in morphology and function of microglia during neuro-inflammatory process.

Key words: adenosine A2A receptor, experimental autoimmune encephalomyelitis, microglia, antagonist

CLC Number:

R965.2

CHEN Yu，YIN Weiyong，CHEN Yanyan，ZHU Zhenguo，ZHENG Rongyuan，ZHENG Liupu. Effects of adenosine A2A receptor antagonist on lipopolysaccharide induced inflammatory BV-2 microglial cells' morphology and function[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1376-1384.

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