Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes
Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes
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DOI：
10.3390/cells8040328
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发表时间：
2019-04-01
期刊：
影响因子：
6
通讯作者：
Moon, Jong-Seok
中科院分区：
文献类型：
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作者：
Bae, Jung Hwan;Jo, Seung, II;Moon, Jong-Seok
线粒体功能障碍与胰岛素抵抗和2型糖尿病的发病机制有关。受损线粒体DNA （mtDNA）可能在2型糖尿病期间调节高血糖中起作用。在患者的血清和血浆中发现了循环无细胞线粒体DNA (ccf-mtDNA)，并与各种人类疾病的预后因素有关。然而，ccf-mtDNA在2型糖尿病慢性炎症中的作用尚不清楚。在这项研究中，我们假设ccf-mtDNA水平与2型糖尿病患者的慢性炎症有关。与健康受试者相比，2型糖尿病患者血浆中的mtDNA水平升高。2型糖尿病患者mtDNA水平升高与白细胞介素-1 （IL-1）水平相关。来自2型糖尿病患者的mtDNA诱导黑色素瘤2 （AIM2）炎症小体依赖性caspase-1激活和巨噬细胞IL-1和IL-18分泌缺失。我们的研究结果表明，ccf-mtDNA可能有助于AIM2炎症小体介导的2型糖尿病慢性炎症。
Mitochondrial dysfunction has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. Damaged mitochondria DNA (mtDNA) may have a role in regulating hyperglycemia during type 2 diabetes. Circulating cell-free mitochondria DNA (ccf-mtDNA) was found in serum and plasma from patients and has been linked to the prognosis factors in various human diseases. However, the role of ccf-mtDNA in chronic inflammation in type 2 diabetes is unclear. In this study, we hypothesized that the ccf-mtDNA levels are associated with chronic inflammation in patients with type 2 diabetes. The mtDNA levels were elevated in the plasma from patients with type 2 diabetes compared to healthy subjects. The elevated mtDNA levels were associated with interleukin-1 (IL-1) levels in patients with type 2 diabetes. The mtDNA, from patients with type 2 diabetes, induced absent in melanoma 2 (AIM2) inflammasome-dependent caspase-1 activation and IL-1 and IL-18 secretion in macrophages. Our results suggest that the ccf-mtDNA might contribute to AIM2 inflammasome-mediated chronic inflammation in type 2 diabetes.