循环无细胞 mtDNA 导致 2 型糖尿病患者的 AIM2 炎性体介导的慢性炎症。
Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes.
机构信息
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea.
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea.
出版信息
Cells. 2019 Apr 8;8(4):328. doi: 10.3390/cells8040328.
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)β 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-1β 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.
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。受损的线粒体 DNA（mtDNA）可能在 2 型糖尿病期间调节高血糖方面发挥作用。来自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 型糖尿病患者的血浆中 mtDNA 水平升高。升高的 mtDNA 水平与 2 型糖尿病患者的白细胞介素-1（IL-1）β水平相关。来自 2 型糖尿病患者的 mtDNA 诱导黑色素瘤缺失 2（AIM2）炎性体依赖性半胱天冬酶-1 激活以及巨噬细胞中白细胞介素-1β和白细胞介素-18 的分泌。我们的结果表明，ccf-mtDNA 可能有助于 2 型糖尿病中 AIM2 炎性体介导的慢性炎症。
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