Effect of apolipoprotein E on matrix metalloproteinases-9 expression and its mechanism in astrocytes
10.3760/cma.j.issn.1671-8925.2017.04.006
- VernacularTitle:载脂蛋白E对星形胶质细胞基质金属蛋白酶-9表达的作用及机制研究
- Author:
Wenyu LU
1
;
Yulan TANG
;
Yifeng LI
;
Lijun FAN
;
Junjie WEI
;
Minghua ZHENG
;
Yunfei WEI
;
Daobin CHENG
Author Information
1. 广西医科大学第一附属医院神经内科
- Keywords:
Apolipoprotein E;
Astrocyte;
Matrix metalloproteinases-9;
Tissue inhibitor of metalloproteinase-1;
Blood brain barrier
- From:
Chinese Journal of Neuromedicine
2017;16(4):349-354
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of apolipoprotein E (ApoE) on matrix metalloproteinases-9 (MMP-9) expression and its mechanism in astrocytes.Methods (1) Astrocytes in ApoE gene knock out (ApoE-/-) and wild type (WT) C57BL/6J suckling mice were cultured in vitro;glial fibrillary acidic protein antibodies were employed to identify the astrocytes;MMP-9.antibodies were employed to detect the MMP-9 expression in the astrocytes.(2) Astrocytes from the ApoE-/-and wild type WT C57BL/6J suckling mice were divided into activation group,antibody groups and control group randomly;cells in the control group did not give any treatment;cells in the activation group were given whooping cough toxin and thermal inactivation-mycobacterium tuberculosis H37Ra;cells in the antibody groups were given anti-interleukin-6 (IL-6),interferon gamma (IFN--γ),tumor necrosis factor-α (TNF-α) and IL-12,respectively,to inhibit their inflammatory factors.ELISA was performed to detect the concentrations of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1),and the inflammatory factors concentrations ofTNF-,IL-12,IL-6,and IFN-γ.Results These two kinds of rat astrocytes could both qualitatively express MMP-9;as compared with the control group,the activation group had significantly higher MMP-9 concentration (P＜0.05);the activation group had significantly higher MMP-9 concentration as compared with the antibody groups (P＜0.05);activation group from ApoE-/-C57BL/6J suckling mice had significantly higher MMP-9 concentration than that from wild type C57BL/6J suckling mice (P＜0.05).The concentration of TIMP-1 was not significantly different among various groups (P＞0.05).The concentrations of inflammatory factors in the activation groups from two kinds of mice were significantly higher than those in the control group (P＜0.05);the concentrations of IL-6,IFN-γ TNF-α and IL-12 in each antibody group were significantly lower than those in the activated group (P＜0.05);the concentrations of inflammatory factors in ApoE-/-rats were significantly higher than those in WT rats (P＜0.05).Conclusion ApoE can regulate the MMP-9 expression by regulating the secretion of proinflammatory cytokines,which can affect the integrity of blood brain barrier.
