HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome

Shinkichi Takamori, Fumihiro Shoji, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Masakazu Katsura, Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Yoshihiko Maehara

Research output: Contribution to journalArticle

Abstract

Background: Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. Methods: A murine heterotopic tracheal transplantation model was used. Protein concentrations of HMGB1, interferon-γ (IFN-γ), interleukin (IL)-10, and IL-17 were analyzed in the isografts, allografts, controls, and HMGB1-neutralizing antibody administered allografts (n = 6; Days 1, 3, 5, 7, 14, 21, and 28). The luminal fibrous occlusion was analyzed (n = 6; Days 7, 14, 21, and 28). Infiltrating CD8 and CD4 T lymphocytes around the allografts and serum levels of IFN-γ and IL-10 were evaluated (n = 6; Day 7). Results: The HMGB1 levels in the allografts were significantly increased compared with the isografts at Day 7. HMGB1 blockade did not change the IL-17 level, but decreased the IFN-γ/IL-10 ratio in the early phase (Days 5 and 7) and significantly improved the fibrous occlusion in the late phase (Days 14, 21, and 28). HMGB1 blockade significantly suppressed the CD8 T lymphocytes infiltration and decreased the serum IFN-γ/IL-10 ratio compared with the control at Day 7. Conclusions: HMGB1 may be a trigger of the BOS pathogenesis and candidate target for the treatment of the disease.

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalTransplant Immunology
Volume53
DOIs
Publication statusPublished - Apr 1 2019

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Bronchiolitis Obliterans
Interleukin-10
Interferons
Allografts
Isografts
Interleukin-17
Heterotopic Transplantation
HMGB1 Protein
T-Lymphocytes
Nuclear Proteins
Neutralizing Antibodies
Serum
Transplantation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Transplantation

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HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome. / Takamori, Shinkichi; Shoji, Fumihiro; Okamoto, Tatsuro; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Akamine, Takaki; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Tagawa, Tetsuzo; Maehara, Yoshihiko.

In: Transplant Immunology, Vol. 53, 01.04.2019, p. 13-20.

Research output: Contribution to journalArticle

Takamori, S, Shoji, F, Okamoto, T, Kozuma, Y, Matsubara, T, Haratake, N, Akamine, T, Katsura, M, Takada, K, Toyokawa, G, Tagawa, T & Maehara, Y 2019, 'HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome', Transplant Immunology, vol. 53, pp. 13-20. https://doi.org/10.1016/j.trim.2018.11.007
Takamori, Shinkichi ; Shoji, Fumihiro ; Okamoto, Tatsuro ; Kozuma, Yuka ; Matsubara, Taichi ; Haratake, Naoki ; Akamine, Takaki ; Katsura, Masakazu ; Takada, Kazuki ; Toyokawa, Gouji ; Tagawa, Tetsuzo ; Maehara, Yoshihiko. / HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome. In: Transplant Immunology. 2019 ; Vol. 53. pp. 13-20.
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AU - Takamori, Shinkichi

AU - Shoji, Fumihiro

AU - Okamoto, Tatsuro

AU - Kozuma, Yuka

AU - Matsubara, Taichi

AU - Haratake, Naoki

AU - Akamine, Takaki

AU - Katsura, Masakazu

AU - Takada, Kazuki

AU - Toyokawa, Gouji

AU - Tagawa, Tetsuzo

AU - Maehara, Yoshihiko

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AB - Background: Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. Methods: A murine heterotopic tracheal transplantation model was used. Protein concentrations of HMGB1, interferon-γ (IFN-γ), interleukin (IL)-10, and IL-17 were analyzed in the isografts, allografts, controls, and HMGB1-neutralizing antibody administered allografts (n = 6; Days 1, 3, 5, 7, 14, 21, and 28). The luminal fibrous occlusion was analyzed (n = 6; Days 7, 14, 21, and 28). Infiltrating CD8 and CD4 T lymphocytes around the allografts and serum levels of IFN-γ and IL-10 were evaluated (n = 6; Day 7). Results: The HMGB1 levels in the allografts were significantly increased compared with the isografts at Day 7. HMGB1 blockade did not change the IL-17 level, but decreased the IFN-γ/IL-10 ratio in the early phase (Days 5 and 7) and significantly improved the fibrous occlusion in the late phase (Days 14, 21, and 28). HMGB1 blockade significantly suppressed the CD8 T lymphocytes infiltration and decreased the serum IFN-γ/IL-10 ratio compared with the control at Day 7. Conclusions: HMGB1 may be a trigger of the BOS pathogenesis and candidate target for the treatment of the disease.

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