Activated peroxisome proliferator-activated receptor αinhibiting the lipopolysaccharide-induced macrophage-mediated inflammatory responses by promoting the autophagy
10.3760/cma.j.issn.0254-5101.2015.06.007
- VernacularTitle:过氧化物酶体增殖物激活受体α（PPARα）对脂多糖刺激巨噬细胞引发炎症反应的影响
- Author:
Rongrong YANG
;
Li ZHANG
;
Xiangying ZHANG
;
Hongbo SHI
;
Dexi CHEN
;
Zhongping DUAN
;
Feng REN
;
Qi WANG
- Publication Type:Journal Article
- Keywords:
Peroxisome proliferator-activated receptor α;
Autophagy;
Inflammatory response;
Macrophages;
Lipopolysaccharide
- From:
Chinese Journal of Microbiology and Immunology
2015;(6):431-435
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of peroxisome proliferator-activated receptor α( PPARα) on macrophage-mediated inflammatory responses with the interference of lipopolysaccharide and the possible mechanism.Methods The bone marrow stem cells were isolated from the femora of mice.The granulocyte-macrophage colony stimulating factor ( GM-CSF) was used to stimulate the in vitro differentiation from bone marrow stem cells into primary macrophages.An in vitro model with cultured cells expressing in-flammatory cytokines was established by treating the primary macrophages with lipopolysaccharide ( LPS) .A specific chemical agonist, Wy-14643, was used to activate PPARα. Autophagy inhibitors including 3-methyladenine (3-MA) and small interfering RNA against Atg7 ( Atg7 siRNA) were used to inhibit the autophagy.Western blot assay was performed to detect the expression of autophagy-related proteins ( Atg5, Atg7, Beclin-1 and LC3).The transcriptional levels of TNF-α, IL-1β, IL-6, Atg5, Atg7 and Beclin-1 were analyzed by qRT-PCR.Results Compared with the macrophages treated with LPS alone, those pretreated with various concentrations of Wy-14643 (10 μmol/L, 25 μmol/L and 50 μmol/L) showed inhibited ex-pression of proinflammatory cytokines ( TNF-α,IL-1βand IL-6) and enhanced expression of autophagy-relat-ed proteins (Atg5, Atg7 and Beclin-1) at mRNA level in a dose-dependent manner.The expression of auto-phagy-related proteins (Atg5, Atg7, Beclin-1 and LC3) by macrophages was promoted with the pretreatment of Wy-14643 as indicated by Western blot assay.The transcriptional levels of TNF-α, IL-1βand IL-6 were increased in Wy-14643 pretreated-macrophages after stimulation with 3-MA or Atg7 siRNA .Conclusion PPARαsuppressed the macrophage-mediated inflammatory responses by promoting autophagy, suggesting that the PPARα-autophagy pathway might be one of the signaling pathways regulating LPS induced-inflamma-tory responses.
