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2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells
- 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.
- Subjects :
- MAP Kinase Kinase 4
Malates
RPE cells
Pharmaceutical Science
Organic chemistry
Inflammation
Retinal Pigment Epithelium
Ciliopathies
Retina
Article
Analytical Chemistry
Proinflammatory cytokine
primary cilia
QD241-441
Ciliogenesis
Drug Discovery
medicine
Humans
Cilia
Physical and Theoretical Chemistry
Retinal pigment epithelium
Chemistry
Cilium
Epithelium
particulate matter (PM2.5)
Cell biology
Enzyme Activation
Oxidative Stress
medicine.anatomical_structure
Chemistry (miscellaneous)
inflammation
Gene Knockdown Techniques
Molecular Medicine
Cytokines
Particulate Matter
2-IPMA
sense organs
medicine.symptom
Reactive Oxygen Species
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 5409
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....4a319e66ebe8b9e17e9e0f0ad144a1e8