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

Authors :
Yong Hwan Kim
Ha Jung Lee
Hye-Won Na
Doo Sin Jo
Ji-Eun Bae
Hong Bae Jeon
Hong-Yeoul Ryu
Dong-Hyung Cho
Sohyun Kim
Hyungjung Choi
Zae Young Ryoo
Ji Yeon Choi
Joon Bum Kim
Seong Hyun Kim
Na Yeon Park
Hyun-Shik Lee
Source :
Molecules, Vol 26, Iss 5409, p 5409 (2021), Molecules, Volume 26, Issue 17
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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.

Details

Language :
English
ISSN :
14203049
Volume :
26
Issue :
5409
Database :
OpenAIRE
Journal :
Molecules
Accession number :
edsair.doi.dedup.....4a319e66ebe8b9e17e9e0f0ad144a1e8