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2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells
Authors:Ji Yeon Choi  Ji-Eun Bae  Joon Bum Kim  Doo Sin Jo  Na Yeon Park  Yong Hwan Kim  Ha Jung Lee  Seong Hyun Kim  So Hyun Kim  Hong Bae Jeon  Hye-Won Na  Hyungjung Choi  Hong-Yeoul Ryu  Zae Young Ryoo  Hyun-Shik Lee  Dong-Hyung Cho
Institution:1.BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Korea; (J.Y.C.); (J.B.K.); (D.S.J.); (N.Y.P.); (Y.H.K.); (H.J.L.); (S.H.K.); (S.H.K.); (H.-Y.R.); (Z.Y.R.); (H.-S.L.);2.Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea;3.Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea;4.R&D Center AMOREPACIFIC Corporation, Yongin 17074, Gyeonggi-do, Korea; (H.-W.N.); (H.C.)
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.
Keywords:primary cilia  2-IPMA  particulate matter (PM2  5)  inflammation  RPE cells
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