Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes
Jung Hwan Bae,
Seung Jo,
Seong Jin Kim,
Jong Min Lee,
Ji Hun Jeong,
Jeong Suk Kang,
Nam-Jun Cho,
Sang Soo Kim,
Eun Young Lee,
Jong-Seok Moon
Affiliations
Jung Hwan Bae
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
Seung Jo
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
Seong Jin Kim
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
Jong Min Lee
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
Ji Hun Jeong
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
Jeong Suk Kang
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea
Nam-Jun Cho
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea
Sang Soo Kim
Department of Internal Medicine, Pusan National University Hospital, Pusan 50612, Korea
Eun Young Lee
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea
Jong-Seok Moon
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 31151, Korea
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.
