Activation of TRPV4 Channel Regulates Differentiation to and Function of Myeloid-Derived Suppressor Cells

DOI Web Site 参考文献28件
  • Yamamoto Moeka
    Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Horie Ichiro
    Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science Division of Systems Immunology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University
  • Isohama Yoichiro
    Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Tsukimoto Mitsutoshi
    Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science

この論文をさがす

抄録

<p>Myeloid-derived suppressor cells (MDSCs), which are derived from immature bone marrow cell (BMC) populations that proliferate in the tumor microenvironment, suppress T cell immune responses. Transient receptor potential vanilloid (TRPV) 4, which is a Ca2+ channel, is involved in tumor growth, but the role of TRP channels in MDSC differentiation and function remains unclear. Here, we first investigated the involvement of TRP channels in the differentiation of MDSCs. The selective TRPV4 channel antagonist RN-1734 increased the population of MDSCs (CD11b+Gr-1+) at Day 3, while the TRPV4 agonist GSK1016790A decreased it, suggesting that stimulation of TRPV4 suppresses the differentiation of BMCs to MDSCs. GSK1016790A also increased the production of nitric oxide and reactive oxygen species, but suppressed the expression of Arg-1 mRNA, which encodes arginase-1, in MDSCs. Furthermore, GSK1016790A decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MDSCs, thereby attenuating STAT3 signaling. Our results suggest that TRPV4 plays a role in regulating both the differentiation and function of MDSCs, and therefore could be a promising target for cancer immunotherapy.</p>

収録刊行物

  • BPB Reports

    BPB Reports 3 (2), 70-75, 2020

    公益社団法人 日本薬学会

参考文献 (28)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ