International Journal of Stem Cells

  • 제15권2호
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  • Pages.203-216
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  • 2022
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  • 2005-3606(pISSN)
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  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
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Diesel Exhaust Particles Impair Therapeutic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis through ROS/ERK/cFos Signaling Pathway

  • Hyun Sung Park (Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea) ;
  • Mi-Kyung Oh (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Joong Won Lee (Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health) ;
  • Dong-Hoon Chae (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Hansol Joo (Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea) ;
  • Ji Yeon Kang (Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea) ;
  • Hye Bin An (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Aaron Yu (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Jae Han Park (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University) ;
  • Hee Min Yoo (Biometrology Group, Korea Research Institute of Standards and Science (KRISS)) ;
  • Hyun Jun Jung (Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine) ;
  • Uimook Choi (Laboratory of Clinical Immunology and Microbiology, NIAID, NIH) ;
  • Ji-Won Jung (Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health) ;
  • In-Sook Kim (Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea) ;
  • Il-Hoan Oh (Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea) ;
  • Kyung-Rok Yu (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University)
  • 투고 : 2021.10.06
  • 심사 : 2021.11.10
  • 발행 : 2022.05.30
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초록

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 ㎍/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 ㎍/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

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과제정보

This research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) (2019R1C1C1008896) funded by the Korean government.

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