Soluble recombinant human thrombomodulin suppresses inflammation-induced gastrointestinal tumor growth in a murine peritonitis model

En Amada, Kazumasa Fukuda, Koshi Kumagai, Hirofumi Kawakubo, Yuko Kitagawa

研究成果: Article査読

抄録

Regulatory T cells (Tregs) and transforming growth factor β (TGF-β) are believed to play key roles in both postoperative pro-inflammatory and anti-inflammatory responses of malignancies. Recombinant human thrombomodulin (rTM) is implied to inhibit the interaction between TGF-β and Tregs. The aim of this study is to evaluate the antitumor effects of rTM against gastrointestinal tumors under systemic inflammation. Mice were subjected to cecal ligation and puncture and percutaneous allogeneic tumor implantation. rTM were introduced by percutaneous injection into the abdominal cavity. The effects of rTM were evaluated by weight of implanted tumor, proportion of Tregs in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and temporal evaluation of serum cytokines. The effect of rTM was also evaluated on the in vitro differentiation of naïve T cells into induced Tregs induced by TGF-β and interleukin (IL) -2. rTM significantly inhibited the proliferation of the implanted tumor cells in an inflammation-dependent manner. rTM also reduced the fractions of regulatory T cells and induced regulatory T cells among both PBL and TIL. Temporal evaluation of serum cytokine levels in the model mice showed that rTM significantly suppressed the increases in the serum levels of IL-2 and TGF-β. An in vitro differentiation assay revealed that rTM inhibited the differentiation of naïve T cells into Tregs triggered by IL-2- and TGF-β. rTM has suppressive effects on inflammation-induced gastrointestinal tumor growth by suggestively affecting differentiation of Tregs.

本文言語English
ページ(範囲)195-203
ページ数9
ジャーナルMolecular and Cellular Biochemistry
475
1-2
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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