JMJD3 Is Required for Acute Pancreatitis and Pancreatitis- Associated Lung Injury

被引：11

作者：

Chen, Li ^{[1
]}

Zhang, Xiangxian ^{[1
]}

Liu, Yu ^{[1
]}

Liu, Li ^{[1
]}

Liang, Xiao ^{[1
]}

Yang, Shengqun ^{[1
]}

Xia, Qing ^{[2
]}

Jin, Tao ^{[2
]}

Ma, Yun ^{[2
]}

Chen, Yonghua ^{[3
]}

Yuan, Xia ^{[1
]}

Tie, Yan ^{[1
]}

Gu, Yangzhuo ^{[1
]}

Fang, Chunju ^{[1
]}

Chen, Siyuan ^{[1
]}

Mo, Fei ^{[1
]}

Yu, Ting ^{[1
]}

Hu, Yuzhu ^{[1
]}

Qian, Zhiyong ^{[1
]}

Peng, Yong ^{[1
]}

Geng, Jia ^{[1
]}

Zhou, Zongguang ^{[4
]}

Wu, Min ^{[5
]}

Ding, Jiansheng ^{[6
]}

Yang, Daoke ^{[6
]}

Wei, Xiawei ^{[1
,7
]}

机构：

[1] Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Lab Aging Res & Nanotoxicol,State Key Lab Biothera, Chengdu, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, Dept Integrated Tradit Chinese & Western Med, Chengdu, Sichuan, Peoples R China

[3] Sichuan Univ, West China Hosp, Pancreat Dis Ctr, Dept Pancreat Surg, Chengdu, Sichuan, Peoples R China

[4] Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, Chengdu, Sichuan, Peoples R China

[5] Univ North Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND USA

[6] Zhengzhou Univ, Affiliated Hosp 1, Dept Radiotherapy, Zhengzhou, Peoples R China

[7] Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Lab Aging Res & Nanotoxicol, 17 Block 3 Southern Renmin Rd, Chengdu 610041, Sichuan, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2023年 / 210卷 / 02期

关键词：

OXIDIZED MITOCHONDRIAL-DNA; PRO-INFLAMMATORY CYTOKINES; OXIDATIVE DAMAGE; CELL NECROSIS; IN-VITRO; MACROPHAGES; RESPONSES; PATHWAY; MODEL;

D O I：

10.4049/jimmunol.2200484

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-kB-JMJD3-TNF-a pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury. The

引用

页码：180 / 190

页数：12

共 56 条

[1] UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development [J].