Role of peroxisome proliferator-activated receptor-γ in secretion of inflammatory cytokine and migration of N9 microglia cells induced by hypoxia
10.3760/cma.j.issn.1671-8925.2017.01.008
- VernacularTitle:激活PPAR-γ对缺氧诱导的N9小胶质细胞迁移和炎症因子释放能力的影响
- Author:
Li CHONG
1
;
Peng TANG
;
Peng LIU
;
Li CHEN
;
Yue LIU
;
Rui LI
;
Minxia GUO
Author Information
1. 陕西省人民医院神经内科
- Keywords:
Microglia;
Peroxisome proliferator-activated receptor-γ;
Hypoxia inducible factor-1α;
Inflammation mediator;
Cell migration
- From:
Chinese Journal of Neuromedicine
2017;16(1):40-45
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role ofperoxisome proliferator-activated receptor (PPAR)-γ in hypoxia-induced secretion of inflammatory cytokine and migration of N9 microglia cells by activating PPAR-γsignaling with pioglitazone and its mechanism.Methods N9 microglia cells cultured in vitro were divided into normoxia group,hypoxia group,pioglitazone+hypoxia group and T0070907 (PPAR-γ pathway inhibitor)+pioglitazone+hypoxia group.Total cell RNA and protein were prepared,Western blotting was employed to detect the protein expressions of hypoxia-inducible factor-1 (HIF-1α).Real-time PCR was used to detect the interleukin (IL)-1 β,IL-6 and TNF-α mRNA expressions.The migration ability of N9 cells was detected by Transwell assay.The HIF-1α protein expression in N9 cells was detected by immunofluorescence.Results As compared with cells from normoxia group,cells from the hypoxia group had significantly increased HIF-1α protein expression,markedly enhanced migration ability and significantly increased mRNA levels of IL-1β,IL-6 and TNF-α (P＜0.05).As compared with those in the cells from the hypoxia group,the HIF-1α protein expression,migration ability and IL-1β,IL-6 and TNF-α mRNA levels were significantly decreased in the cells from pioglitazone+hypoxia group (P＜ 0.05).T0070907+pioglitazone+hypoxia group had significantly increased HIF-1α protein expression,migration ability and IL-1β,IL-6 and TNF-o mRNA levels as compared with pioglitazone+hypoxia group (P＜0.05).Conclusion Activation of PPAR-γ pathway could inhibit the hypoxia-induced secretion of inflammatory cytokine and migration ability of N9 microglia cells via down-regulation of HIF-1α protein and IL-1β,IL-6 and TNF-α mRNA expressions.
