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

1
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
2
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea
3
Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea
4
Department of Internal Medicine, Pusan National University Hospital, Pusan 50612, Korea
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(4), 328; https://doi.org/10.3390/cells8040328
Received: 7 February 2019 / Revised: 3 April 2019 / Accepted: 6 April 2019 / Published: 8 April 2019
(This article belongs to the Special Issue Mechanisms of Inflammasome Activation)
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Abstract

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. View Full-Text
Keywords: ccf-mtDNA; chronic inflammation; AIM2 inflammasome; type 2 diabetes ccf-mtDNA; chronic inflammation; AIM2 inflammasome; type 2 diabetes
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Bae, J.H.; Jo, S., II; Kim, S.J.; Lee, J.M.; Jeong, J.H.; Kang, J.S.; Cho, N.-J.; Kim, S.S.; Lee, E.Y.; Moon, J.-S. Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes. Cells 2019, 8, 328.

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