2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells

Molecules

卷:26

Ha Jung Lee¹  Seong Hyun Kim¹  Yong Hwan Kim¹  Hong-Yeoul Ryu¹  So Hyun Kim¹  Dong-Hyung Cho¹  Ji Yeon Choi¹  Zae Young Ryoo¹  Hyun-Shik Lee¹  Joon Bum Kim¹  Na Yeon Park¹  Doo Sin Jo¹  Ji-Eun Bae²  Hye-Won Na³  Hyungjung Choi³  Hong Bae Jeon⁴ 

[1] BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Korea;

[2] Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea;

[3] R&D Center AMOREPACIFIC Corporation, Yongin 17074, Gyeonggi-do, Korea;

[4] Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea;

关键词: primary cilia;    2-IPMA;    particulate matter (PM2.5);    inflammation;    RPE cells;   

DOI  :  10.3390/molecules26175409

来源: DOAJ

【 摘 要 】

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

【 授权许可】

Unknown