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

被引：135

作者：

Bae, Jung Hwan ^{[1
]}

Jo, Seung, II ^{[1
]}

Kim, Seong Jin ^{[1
]}

Lee, Jong Min ^{[1
]}

Jeong, Ji Hun ^{[1
]}

Kang, Jeong Suk ^{[2
,3
]}

Cho, Nam-Jun ^{[2
]}

Kim, Sang Soo ^{[4
]}

Lee, Eun Young ^{[2
,3
]}

Moon, Jong-Seok ^{[1
]}

机构：

[1] Soonchunhyang Univ, SIMS, Dept Integrated Biomed Sci, Cheonan Si 31151, Chungcheongnam, South Korea

[2] Soonchunhyang Univ, Cheonan Hosp, Dept Internal Med, Cheonan 31151, South Korea

[3] Soonchunhyang Univ, Inst Tissue Regenerat, Coll Med, Cheonan 31151, South Korea

[4] Pusan Natl Univ Hosp, Dept Internal Med, Pusan 50612, South Korea

来源：

CELLS | 2019年 / 8卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

ccf-mtDNA; chronic inflammation; AIM2; inflammasome; type; 2; diabetes; FREE MITOCHONDRIAL-DNA; PLASMA NUCLEAR; RELEASE; DAMAGE; ACTIVATION; BIOMARKER; DISEASE; NEPHROPATHY; DYSFUNCTION; MECHANISM;

D O I：

10.3390/cells8040328

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页数：12

共 48 条

[1]

The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis [J].

Algaba-Chueca, Francisco ;

de-Madaria, Enrique ;

Lozano-Ruiz, Beatriz ;

Martinez-Cardona, Claudia ;

Quesada-Vazquez, Noe ;

Bachiller, Victoria ;

Tarin, Fabian ;

Such, Jose ;

Frances, Ruben ;

Zapater, Pedro ;

Gonzalez-Navajas, Jose M. .

PANCREATOLOGY, 2017, 17 (03) :364-371

[2]

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient [J].

Alvarado-Vasquez, Noe .

EXPERIMENTAL GERONTOLOGY, 2015, 69 :70-78

[3]

Increased circulating mitochondrial DNA after myocardial infarction [J].

Bliksoen, Marte ;

Mariero, Lars Henrik ;

Ohm, Ingrid Kristine ;

Haugen, Fred ;

Yndestad, Arne ;

Solheim, Svein ;

Seljeflot, Ingebjorg ;

Ranheim, Trine ;

Andersen, Geir Oystein ;

Aukrust, Pal ;

Valen, Guro ;

Vinge, Leif Erik .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2012, 158 (01) :132-134

[4]

Circulatory Mitochondrial DNA Is a Pro-Inflammatory Agent in Maintenance Hemodialysis Patients [J].

Cao, Hongdi ;

Ye, Hong ;

Sun, Zhiping ;

Shen, Xia ;

Song, Zongwei ;

Wu, Xiaochun ;

He, Weichun ;

Dai, Chunsun ;

Yang, Junwei .

PLOS ONE, 2014, 9 (12)

[5]

Dampening insulin signaling by an NLRP3 'meta-flammasome' [J].

Choi, Augustine M. K. ;

Nakahira, Kiichi .

NATURE IMMUNOLOGY, 2011, 12 (05) :379-380

[6]

Plasma nuclear DNA and mitochondrial DNA as prognostic markers in corrosive injury patients [J].

Chou, Chu-Chung ;

Fang, Hsin-Yun ;

Chen, Yao-Li ;

Wu, Chin-Yen ;

Siao, Fu-Yuan ;

Chou, Ming-Jen .

DIGESTIVE SURGERY, 2008, 25 (04) :300-304

[7]

Plasma Mitochondrial DNA-a Novel DAMP in Pediatric Sepsis [J].

Di Caro, Valentina ;

Walko, Thomas D., III ;

Bola, R. Aaron ;

Hong, John D. ;

Pang, Diana ;

Hsue, Victor ;

Au, Alicia K. ;

Halstead, E. Scott ;

Carcillo, Joseph A. ;

Clark, Robert S. B. ;

Aneja, Rajesh K. .

SHOCK, 2016, 45 (05) :506-511

[8]

AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity [J].

Di Micco, Antonia ;

Frera, Gianluca ;

Lugrin, Jerome ;

Jamilloux, Yvan ;

Hsu, Erh-Ting ;

Tardivel, Aubry ;

De Gassart, Aude ;

Zaffalon, Lea ;

Bujisic, Bojan ;

Siegert, Stefanie ;

Quadroni, Manfredo ;

Broz, Petr ;

Henry, Thomas ;

Hrycyna, Christine A. ;

Martinon, Fabio .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (32) :E4671-E4680

[9]

Mitochondrial DNA in serum of patients with prostate cancer:: a predictor of biochemical recurrence after prostatectomy [J].

Ellinger, Joerg ;

Mueller, Stefan C. ;

Wernert, Nicolas ;

von Ruecker, Alexander ;

Bastian, Patrick J. .

BJU INTERNATIONAL, 2008, 102 (05) :628-632

[10]

The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis [J].

Franchi, Luigi ;

Eigenbrod, Tatjana ;

Munoz-Planillo, Raul ;

Nunez, Gabriel .

NATURE IMMUNOLOGY, 2009, 10 (03) :241-247

← 1 2 3 4 5 →