Pioglitazone improves phagocytic activity of liver recruited macrophages in elderly mice possibly by promoting glucose catabolism
Pioglitazone improves phagocytic activity of liver recruited macrophages in elderly mice possibly by promoting glucose catabolism
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DOI：
10.1177/1753425919849620
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发表时间：
2019-05
期刊：
影响因子：
3.2
通讯作者：
M. Nakashima;M. Kinoshita;H. Nakashima;A. Kotani;Takuya Ishikiriyama;S. Kato;S. Hiroi;S. Seki
中科院分区：
文献类型：
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作者：
M. Nakashima;M. Kinoshita;H. Nakashima;A. Kotani;Takuya Ishikiriyama;S. Kato;S. Hiroi;S. Seki
最近的研究表明，白细胞的免疫功能依赖于其细胞代谢，一些研究人员主张吡格列酮对年轻小鼠败血症的有益作用，尽管细菌感染在老年宿主中更普遍。在这里，我们研究了吡格列酮对老年小鼠（50-60周龄）静脉注射致死剂量大肠杆菌诱导的脓毒症的预防作用，并检查了其对肝脏白细胞的免疫和代谢作用。吡格列酮改善外周血中的细菌清除，降低血清促炎细胞因子（TNF-α、IL-12、IFN-γ），并预防脓毒性死亡。它还通过增加肝脏F4/80+ CD 11b+募集的巨噬细胞（Mφ）的吞噬和杀菌活性、其CD 206表达和活性氧产生来增强肝脏中的细菌清除。定量PCR显示，吡格列酮处理增强了肝CD 11b+细胞（包括中性粒细胞和募集的Mφ）中糖酵解限速酶的基因表达，并且其增强的吞噬和杀菌活性被糖酵解抑制剂消除。这些发现表明吡格列酮可能增强了肝脏募集的Mφ的吞噬和杀菌活性，并且这些免疫活性与其葡萄糖催化剂密切相关。
Recent studies have revealed that the immunological function of leukocytes is dependent on their cellular metabolism, and some researchers have advocated the beneficial effects of pioglitazone against sepsis in young mice, although bacterial infections are more prevalent in elderly hosts. Here, we investigated pioglitazone’s preventative effect against sepsis induced by intravenous injection of a lethal dose of Escherichia coli in elderly mice (50–60 wk old) and examined its immunological and metabolic effects on liver leukocytes. Pioglitazone improved bacterial elimination in the peripheral blood, lowered serum pro-inflammatory cytokines (TNF-α, IL-12, IFN-γ), and prevented septic death. It also enhanced bacterial elimination in the liver, by increasing the phagocytic and bactericidal activities of liver F4/80+CD11b+ recruited macrophages (Mφ), their CD206 expression and reactive oxygen species production. Quantitative PCR revealed that pioglitazone treatment enhanced gene expression of rate-limiting enzymes for glycolysis in hepatic CD11b+ cells (including neutrophils and recruited Mφ), and their improved phagocytic and bactericidal activities were abolished by glycolysis inhibiting reagents. These findings present the possibility that pioglitazone strengthens the phagocytic and bactericidal activities of liver recruited Mφ and that these immunological activities are closely associated with their glucose catabolism.