Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model |
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Authors: | Ji-Eun Bae Daejin Min Ji Yeon Choi Hyunjung Choi Joon Bum Kim Na Yeon Park Doo Sin Jo Yong Hwan Kim Hye-Won Na Yoon Jae Kim Eun Sung Kim Hyoung-June Kim Dong-Hyung Cho |
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Affiliation: | 1.Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea;2.R&D Center, AMOREPACIFIC Corporation, Yongin 17074, Korea; (D.M.); (H.C.); (H.-W.N.);3.School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea; (J.Y.C.); (J.B.K.); (N.Y.P.); (D.S.J.); (Y.H.K.); (Y.J.K.);4.New Drug Development Center, Osong Medical Innovation Foundation, Cheongju 28160, Korea; |
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Abstract: | Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts. |
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Keywords: | 2-IPMA primary cilia dermal fibroblasts oxidative stress inflammation |
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