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- Title
2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells.
- Authors
Choi, Ji Yeon; Bae, Ji-Eun; Kim, Joon Bum; Jo, Doo Sin; Park, Na Yeon; Kim, Yong Hwan; Lee, Ha Jung; Kim, Seong Hyun; Kim, So Hyun; Jeon, Hong Bae; Na, Hye-Won; Choi, Hyungjung; Ryu, Hong-Yeoul; Ryoo, Zae Young; Lee, Hyun-Shik; Cho, Dong-Hyung
- Abstract
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.
- Subjects
PARTICULATE matter; REACTIVE oxygen species; RHODOPSIN; PHOTORECEPTORS; RETINAL degeneration; INFLAMMATION
- Publication
Molecules, 2021, Vol 26, Issue 17, p5409
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules26175409