Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 4; p. 328
• Main Authors: Bae, Jung Hwan, Jo, Seung, Kim, Seong Jin, Lee, Jong Min, Jeong, Ji Hun, Kang, Jeong Suk, Cho, Nam-Jun, Kim, Sang Soo, Lee, Eun Young, Moon, Jong-Seok
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.04.2019; MDPI
• Subjects: Aged; AIM2 inflammasome; Alzheimer's disease; Animals; Bone marrow; Cardiovascular disease; Case-Control Studies; Caspase-1; ccf-mtDNA; Cells, Cultured; Chronic illnesses; chronic inflammation; Cloning; Cytokines; Dehydrogenases; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; DNA, Mitochondrial - blood; DNA-Binding Proteins - blood; Enrollments; Female; Health care; Human subjects; Humans; Hyperglycemia; IL-1β; Inflammasomes; Inflammasomes - metabolism; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin resistance; Interleukin 18; Interleukin-18 - blood; Interleukin-1beta - blood; Kidney diseases; Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Manufacturers; Melanoma; Middle Aged; Mitochondrial DNA; Plasma; Proteins; type 2 diabetes; Minneapolis Minnesota; United States > US; type 2 diabetes; AIM2 inflammasome; chronic inflammation; ccf-mtDNA
• ISSN: 2073-4409; 2073-4409
• 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-1β (IL-1β) 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.