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

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.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Takamori S,Shoji F,Okamoto T,Kozuma Y,Matsubara T,Haratake N,Akamine T,Katsura M,Takada K,Toyokawa G,Tagawa T,Maehara Y

doi

10.1016/j.trim.2018.11.007

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

13-20

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(18)30118-7

journal_volume

53

pub_type

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