NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of Inflammation

NF-kappaB 和线粒体信号作为炎症的正向和负向调节剂

• 批准号: 10516935
• 负责人: Michael Karin
• 金额: $ 60.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516935
• 关键词: Alzheimer' s Disease; Attenuated; Cytosol; DNA metabolism; Degenerative polyarthritis; Disease model; Generations; Inflammasome; Inflammation; Instruction; Macrophage; Mitochondria; Mitochondrial DNA; Mus; NF-kappa B; Pathogenesis; Role; Signal Transduction; Testing; inhibitor

See Abstract page RELEVANCE (See instructions): We will continue to study the role of mitochondrial DNA metabolism in NLRP3 inflammasome activation and the effect of NRF2 on macrophage polarization. We will examine whether the pathogenesis of osteoarthritis (OA) and Alzheimer’s disease (AD) in mice is accompanied by oxidized mitochondrial DNA generation, its cleavage and export to the cytosol. We will also test the ability of CMPK2 and Fen1 inhibitors to attenuate NLRP3 inflammasome activation in OA, AD and other disease models.

参见摘要页 相关性（参见说明）： 我们将继续研究线粒体DNA代谢在NLRP3炎症小体激活中的作用 以及NRF2对巨噬细胞极化的影响我们将检查其发病机制。 小鼠骨关节炎 (OA) 和阿尔茨海默病 (AD) 都伴随着氧化的线粒体 DNA 我们还将测试 CMPK2 和 Fen1 的生成、裂解和输出到细胞质的能力。 抑制剂可减弱 OA、AD 和其他疾病模型中 NLRP3 炎性体的激活。

项目成果

The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.

• DOI: 10.15252/embj.201488351
• 发表时间: 2014-11-03
• 期刊: The EMBO journal
• 作者: Charlaftis N;Suddason T;Wu X;Anwar S;Karin M;Gallagher E
• 通讯作者: Gallagher E

Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis.

• DOI: 10.1016/j.immuni.2014.11.009
• 发表时间: 2014-12-18
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Wang, Kepeng;Kim, Min Kyoung;Di Caro, Giuseppe;Wong, Jerry;Shalapour, Shabnam;Wan, Jun;Zhang, Wei;Zhong, Zhenyu;Sanchez-Lopez, Elsa;Wu, Li-Wha;Taniguchi, Koji;Feng, Ying;Fearon, Eric;Grivennikov, Sergei I.;Karin, Michael
• 通讯作者: Karin, Michael

The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis.

• DOI: 10.1084/jem.189.11.1839
• 发表时间: 1999-06-07
• 期刊: The Journal of experimental medicine
• 作者: Li ZW;Chu W;Hu Y;Delhase M;Deerinck T;Ellisman M;Johnson R;Karin M
• 通讯作者: Karin M

IKKα-deficient lung adenocarcinomas generate an immunosuppressive microenvironment by overproducing Treg-inducing cytokines.

• DOI: 10.1073/pnas.2120956119
• 发表时间: 2022-02-08
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Song NY;Li X;Ma B;Willette-Brown J;Zhu F;Jiang C;Su L;Shetty J;Zhao Y;Shi G;Banerjee S;Wu X;Tran B;Nussinov R;Karin M;Hu Y
• 通讯作者: Hu Y

Oxidized mitochondrial DNA: a protective signal gone awry.

• DOI: 10.1016/j.it.2023.01.006
• 发表时间: 2023-02
• 期刊: Trends in immunology
• 影响因子: 16.8
• 作者: Hongxu Xian;Michael Karin