详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during Pseudomonas aeruginosa Infection.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China. [2]Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203. [3]State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing 400042, China. [4]Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. [5]Wuhan University School of Health Sciences, Wuhan, Hubei Province 430071, China. [6]West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China [7]Department of Chemistry, Stanford Cancer Institute, and Chemistry, Engineering and Medicine for Human Health Institute, Stanford University, Stanford, CA 94305.

出处：

DOI：

ISSN：

摘要：

The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises 8-oxo-7,8-dihydroguanine lesions induced in DNA by reactive oxygen species, has been linked to the pathogenesis of lung diseases associated with bacterial infections. A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, we report that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during Pseudomonas aeruginosa (PA14) infection, which is mediated by the KRAS-ERK1-NF-κB signaling pathway. Furthermore, SU0268 induces the release of type I IFN by the mitochondrial DNA-cGAS-STING-IRF3-IFN-β axis, which decreases bacterial loads and halts disease progression. Collectively, our results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection. Copyright © 2020 by The American Association of Immunologists, Inc.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2020]版：

大类 | 2 区

医学

小类 | 2 区免疫学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区免疫学

第一作者：

第一作者机构： [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China. [2]Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203.

通讯作者：

通讯机构： [2]Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203. [4]Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. [7]Department of Chemistry, Stanford Cancer Institute, and Chemistry, Engineering and Medicine for Human Health Institute, Stanford University, Stanford, CA 94305. [*1]Department of Chemistry, Stanford Cancer Institute, and Chemistry, Engineering and Medicine for Human Health Institute, Stanford University, Stanford, CA 94305 [*2]Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [*3]University of North Dakota, 1301 North Columbia Road, P.O. Box 9037, Grand Forks, ND 58203

推荐引用方式(GB/T 7714)：

APA：

MLA：