論文

査読有り 国際誌
2020年5月

Interferon-γ-induced HLA Class II expression on endothelial cells is decreased by inhibition of mTOR and HMG-CoA reductase.

FEBS open bio
  • Akihiro Maenaka
  • ,
  • Iwasaki Kenta
  • ,
  • Akinobu Ota
  • ,
  • Yuko Miwa
  • ,
  • Wataru Ohashi
  • ,
  • Kosei Horimi
  • ,
  • Yutaka Matsuoka
  • ,
  • Masafumi Ohnishi
  • ,
  • Kazuharu Uchida
  • ,
  • Takaaki Kobayashi

10
5
開始ページ
927
終了ページ
936
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/2211-5463.12854

In organ transplantation, donor-specific HLA antibody (DSA) is considered a major cause of graft rejection. Because DSA targets primarily donor-specific human leukocyte antigen (HLA) expressed on graft endothelial cells, the prevention of its expression is a possible strategy for avoiding or salvaging DSA-mediated graft rejection. We examined the effect of various clinically used drugs on HLA class II expression on endothelial cells. Interferon-γ (IFN-γ)-induced HLA class II DR (HLA-DR) was downregulated by everolimus (EVR, 49.1% ± 0.8%; P < 0.01) and fluvastatin (FLU, 33.8% ± 0.6%; P < 0.01). Moreover, the combination of EVR and FLU showed a greater suppressive effect on HLA-DR expression. In contrast, cyclosporine, tacrolimus, mycophenolic acid, and prednisolone did not exhibit any significant suppressive effect. FLU, but not EVR, suppressed mRNA of HLA-DR. Imaging analysis revealed that HLA-DR expressed in cytosol or on the cell surface was repressed by EVR (cytosol: 58.6% ± 4.9%, P < 0.01; cell surface: 80.9% ± 4.0%, P < 0.01) and FLU (cytosol: 19.0% ± 3.4%, P < 0.01; cell surface: 48.3% ± 4.8%, P < 0.01). These data indicated that FLU and EVR suppressed IFN-γ-induced HLA-DR expression at the transcriptional and post-translational level, respectively, suggesting a potential approach for alleviating DSA-related issues in organ transplantation.

リンク情報
DOI
https://doi.org/10.1002/2211-5463.12854
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32237049
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193171

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