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iNSC suppress macrophage-induced inflammation by repressing COX-2

In Vitro Cellular & Developmental Biology - Animal volume 51, pages 157–164 (2015)Cite this article

Abstract

Brain inflammation causes cell damage and death in diseases such as Alzheimer’s and Parkinson’s. In this study, we investigated whether early induced neural stem cells (iNSCs) could protect against cell death after treatment with THP1-derived macrophages. We developed an inflammatory model system with THP1-derived macrophages and cortical neuronal cells and investigated the therapeutic efficacy of iNSC against macrophage-induced inflammation in this model. Apoptosis was confirmed by double immunocytochemistry with NeuN and 4′,6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling. Cortical neuronal cells cultured with iNSCs exhibited fewer apoptotic cells than did cultures without iNSCs. The levels of inflammatory cytokines and vascular endothelial growth factor (VEGF) were analyzed by enzyme-linked immunosorbent assay. Cells cultured with iNSCs had lower levels of inflammatory cytokines and higher VEGF levels than those cultured without iNSCs. Western blot analysis for cyclooxygenase-2 (COX-2) showed a significantly lower level of COX-2 in cells cultured with iNSCs than in those cultured without iNSCs. Thus, early iNSCs administration reduced inflammation associated with neurological recovery, and this effect is mediated by COX-2 regulation. Our results suggest that iNSCs have potential therapeutic relevance, because they display strong anti-inflammatory functions that promote neuroprotection thorough the inflammatory response.

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Acknowledgments

This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI12C0337), Republic of Korea.

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Affiliations

  1. Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea

    Jin Hee Kim & Jangbo Lee

  2. Department of Anatomy, College of Medicine, Korea University, Seoul, Korea

    Woong Sun

  3. Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea

    Dong Wook Han

  4. Department of Neurosurgery, Guro Hospital Korea University, Seoul, Korea

    Hong-Joo Moon

Authors
  1. Jin Hee Kim
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  2. Woong Sun
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  3. Dong Wook Han
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  4. Hong-Joo Moon
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  5. Jangbo Lee
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Correspondence to Jangbo Lee.

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Editor: T. Okamoto

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Kim, J.H., Sun, W., Han, D.W. et al. iNSC suppress macrophage-induced inflammation by repressing COX-2. In Vitro Cell.Dev.Biol.-Animal 51, 157–164 (2015). https://doi.org/10.1007/s11626-014-9816-4

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  • DOI: https://doi.org/10.1007/s11626-014-9816-4

Keywords

  • Induced neural stem cells (iNSCs)
  • Inflammatory
  • Cyclooxygenase-2 (COX-2)