HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti–IL-6R Antibody in Mice

DOI Web Site PubMed 被引用文献10件 参考文献26件 オープンアクセス

書誌事項

公開日
2015-01
資源種別
journal article
DOI
  • 10.1097/mpa.0000000000000188
公開者
Ovid Technologies (Wolters Kluwer Health)

この論文をさがす

説明

The limited success in achieving insulin independence of patients with type 1 diabetes mellitus after islet transplantation from a single donor, mainly due to early loss of transplanted islets, hampers clinical application of islet transplantation. Previously, we have shown in mice that the early loss of transplanted islets in the liver, the site of islet transplantation, is caused by innate immune rejection triggered by high-mobility group box 1 (HMGB1) protein released from transplanted islets. We herein determined whether the HMGB1-mediated early loss of transplanted mouse islets is prevented by anti-interleukin-6 receptor (IL-6R) antibody.The effect of anti-IL-6R antibody on amelioration of hyperglycemia in streptozocin-induced diabetic mice receiving 200 islets into the liver from a single donor was evaluated in association with HMGB1-stimulated interferon-γ production of hepatic mononuclear cells.Hyperglycemia of diabetic mice receiving 200 syngeneic islets was ameliorated with down-regulation of interferon-γ production of hepatic natural killer T cells and neutrophils when anti-IL-6R was administered at the time of transplantation. This beneficial effect was also seen in allografts when alloimmune rejection was prevented by anti-CD4 antibody.These findings demonstrate that anti-IL-6R antibody prevented the early loss of intrahepatic islet grafts with inhibiting HMGB1-induced immune activation after islet transplantation.

収録刊行物

  • Pancreas

    Pancreas 44 (1), 166-171, 2015-01

    Ovid Technologies (Wolters Kluwer Health)

被引用文献 (10)*注記

もっと見る

参考文献 (26)*注記

もっと見る

関連プロジェクト

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