The inhibitory effect of methamphetamine on production of cytokines in RAW264.7 cells stimulated by lipopolysaccharide
- VernacularTitle:甲基苯丙胺对脂多糖刺激RAW264.7细胞产生细胞因子的抑制作用
- Author:
Guofen CAO
1
;
Gaili MENG
;
Yanlin LI
;
Yongai ZHANG
Author Information
- Publication Type:Journal Article
- Keywords: methamphetamine(METH); macrophage; dopamine D3 receptor(D3R); ERK1/2; IL-6; IL-10
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):442-447
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effect of methamphetamine(METH)on production of cytokines in RAW264.7 cells stimulated by lipopolysaccharide(LPS)and to explore the possible mechanism.Methods To study the effect of METH on the production of cytokines by LPS-stimulated RAW264.7 cells,the cells were divided into five groups:blank control group,LPS stimulation group,and three METH intervention groups at different concentrations(20,100,and 200 μmol/L),which were METH/LPS groups.To study the role of the dopamine D3 receptor(D3R)in the process,the D3R antagonist NGB2904 was used,and there were five groups:blank control group,LPS stimulation group,METH/LPS group,NGB2904/LPS group,and NGB2904/METH/LPS group.Cell viability was determined using the MTT assay.The levels of IL-6,IL-10,and TNF-α in the supernatants were determined using ELISA.The expressions of p-ERK1/2 and ERK1/2 were determined by Western blotting.Results Compared with the blank control group,the LPS stimulation group and the METH/LPS group had significantly increased cell viability,IL-6,IL-10,TNF-α,and ERK1/2 phosphorylation(P＜0.05).Compared with the LPS stimulation group,the METH/LPS group showed no obvious change in cell viability(P＞0.05),but significantly decreased levels of IL-6,IL-10,and ERK1/2 phosphorylation(P＜0.05).The inhibitory effect of METH showed a dose-dependent manner,with the highest inhibitory effect at METH 200 μmol/L.Furthermore,after the D3R antagonist was used,the results showed that compared with the LPS stimulation group,the cell activity was not significantly changed(P＞0.05),but the levels of IL-6,IL-10 and ERK1/2 phosphorylation were significantly decreased in the METH/LPS group and the NGB2904/LPS group(P＜0.05).Compared with the METH/LPS group or the NGB2904/LPS group,the levels of IL-6,IL-10 and ERK1/2 phosphorylation were further decreased in the NGB2904/METH/LPS group(P＜0.05).Conclusion METH might inhibit the phosphorylation of ERK1/2,thereby reducing the production of IL-6 and IL-10 in RAW264.7 cells stimulated by LPS.The immunosuppressive effect of METH is similar to the immune effect when D3R is antagonized.
