Related Experiment Video
Updated: Oct 21, 2025
Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography
Published on: July 10, 2018
2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells
Ji Yeon Choi1, Ji-Eun Bae2, Joon Bum Kim1
1BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.
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.
Insights
2-isopropylmalic acid (2-IPMA) promotes primary cilia formation in retinal cells, counteracting damage from particulate matter (PM). This metabolite reduces oxidative stress and inflammation, offering a potential therapeutic strategy for PM-induced retinal injury.
Area of Science:
- Cell Biology
- Environmental Health
- Toxicology
Background:
- Primary cilia are crucial for cellular responses to environmental stress, and their dysfunction is linked to ciliopathies like retinal degeneration.
- Particulate matter (PM) exposure can cause cellular damage through oxidative stress and inflammation, notably disrupting primary cilia in retinal pigment epithelium (RPE) cells.
Purpose of the Study:
- To identify novel compounds that can induce primary ciliogenesis.
- To investigate the potential of 2-isopropylmalic acid (2-IPMA) to restore primary cilia function and mitigate PM-induced damage in RPE cells.
Main Methods:
- Screening of a metabolite library to identify inducers of primary ciliogenesis.
- Treatment of RPE cells with 2-IPMA and exposure to PM2.5.
- Assessment of primary cilia formation, length, reactive oxygen species (ROS) levels, JNK activation, and pro-inflammatory cytokine production (IL-6, TNF-α).
Main Results:
- 2-isopropylmalic acid (2-IPMA) was identified as a novel inducer of primary ciliogenesis, increasing both the number of ciliated cells and primary cilium length.
- 2-IPMA treatment restored PM2.5-induced defects in primary cilia formation in RPE cells.
- 2-IPMA significantly reduced PM2.5-induced excessive ROS generation, JNK activation, and the production of pro-inflammatory cytokines IL-6 and TNF-α.
Conclusions:
- 2-isopropylmalic acid (2-IPMA) promotes primary ciliogenesis in RPE cells.
- 2-IPMA ameliorates PM2.5-induced inflammation by enhancing primary cilia formation and reducing oxidative stress and inflammatory responses.
