The prevention of tracheal graft occlusion using pioglitazone: A mouse tracheal transplant model study

Takao Shigenobu, Takashi Ohtsuka, Masayuki Shimoda

Research output: Contribution to journalArticle

Abstract

Bronchiolitis obliterans (BO), which begins with lymphocytic bronchiolitis (LB), is the most serious manifestations of chronic rejection following lung transplantation. We have evaluated the effects of intraperitoneal administration of pioglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, on LB in mice tracheal transplant model. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Animals were divided into three groups (n = 8), isograft (IG) and allograft with (AGP) or without (AGN) pioglitazone. Occlusion rate (OR) of transplanted trachea, CD3, FoxP3 positive cell infiltration, and cytokine levels in the transplanted grafts were analyzed at day 7. In the AGP group, OR was significantly lower than in the AGN group (p <.01). An average of 305 ± 56, and 317 ± 84 CD3-positive T-cells/section was shown in the AGN and AGP groups, respectively (p =.761). Interestingly, an average of 24 ± 18, and 88 ± 28 FoxP3-positive regulatory T-cells (Tregs)/section was shown in AGN and AGP groups, respectively (p =.001). FoxP3 and IL-4 mRNA expression was significantly higher in the AGP group. Pioglitazone can suppress the luminal occlusions of the tracheal graft in an allograft through enhanced Treg infiltration, and may provide new therapies to prevent BO.

Original languageEnglish
JournalTransplant Immunology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

pioglitazone
Bronchiolitis Obliterans
Transplants
Bronchiolitis
Allografts
Isografts
Lung Transplantation
PPAR gamma
Regulatory T-Lymphocytes
Trachea
Interleukin-4
Cytokines
T-Lymphocytes
Messenger RNA

Keywords

  • Bronchiolitis obliterans
  • Lung transplantation
  • Rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

The prevention of tracheal graft occlusion using pioglitazone : A mouse tracheal transplant model study. / Shigenobu, Takao; Ohtsuka, Takashi; Shimoda, Masayuki.

In: Transplant Immunology, 01.01.2018.

Research output: Contribution to journalArticle

@article{20f7a3ed35e8424a9553477dffb75d8c,
title = "The prevention of tracheal graft occlusion using pioglitazone: A mouse tracheal transplant model study",
abstract = "Bronchiolitis obliterans (BO), which begins with lymphocytic bronchiolitis (LB), is the most serious manifestations of chronic rejection following lung transplantation. We have evaluated the effects of intraperitoneal administration of pioglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, on LB in mice tracheal transplant model. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Animals were divided into three groups (n = 8), isograft (IG) and allograft with (AGP) or without (AGN) pioglitazone. Occlusion rate (OR) of transplanted trachea, CD3, FoxP3 positive cell infiltration, and cytokine levels in the transplanted grafts were analyzed at day 7. In the AGP group, OR was significantly lower than in the AGN group (p <.01). An average of 305 ± 56, and 317 ± 84 CD3-positive T-cells/section was shown in the AGN and AGP groups, respectively (p =.761). Interestingly, an average of 24 ± 18, and 88 ± 28 FoxP3-positive regulatory T-cells (Tregs)/section was shown in AGN and AGP groups, respectively (p =.001). FoxP3 and IL-4 mRNA expression was significantly higher in the AGP group. Pioglitazone can suppress the luminal occlusions of the tracheal graft in an allograft through enhanced Treg infiltration, and may provide new therapies to prevent BO.",
keywords = "Bronchiolitis obliterans, Lung transplantation, Rejection",
author = "Takao Shigenobu and Takashi Ohtsuka and Masayuki Shimoda",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.trim.2018.12.002",
language = "English",
journal = "Transplant Immunology",
issn = "0966-3274",
publisher = "Elsevier",

}

TY - JOUR

T1 - The prevention of tracheal graft occlusion using pioglitazone

T2 - A mouse tracheal transplant model study

AU - Shigenobu, Takao

AU - Ohtsuka, Takashi

AU - Shimoda, Masayuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Bronchiolitis obliterans (BO), which begins with lymphocytic bronchiolitis (LB), is the most serious manifestations of chronic rejection following lung transplantation. We have evaluated the effects of intraperitoneal administration of pioglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, on LB in mice tracheal transplant model. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Animals were divided into three groups (n = 8), isograft (IG) and allograft with (AGP) or without (AGN) pioglitazone. Occlusion rate (OR) of transplanted trachea, CD3, FoxP3 positive cell infiltration, and cytokine levels in the transplanted grafts were analyzed at day 7. In the AGP group, OR was significantly lower than in the AGN group (p <.01). An average of 305 ± 56, and 317 ± 84 CD3-positive T-cells/section was shown in the AGN and AGP groups, respectively (p =.761). Interestingly, an average of 24 ± 18, and 88 ± 28 FoxP3-positive regulatory T-cells (Tregs)/section was shown in AGN and AGP groups, respectively (p =.001). FoxP3 and IL-4 mRNA expression was significantly higher in the AGP group. Pioglitazone can suppress the luminal occlusions of the tracheal graft in an allograft through enhanced Treg infiltration, and may provide new therapies to prevent BO.

AB - Bronchiolitis obliterans (BO), which begins with lymphocytic bronchiolitis (LB), is the most serious manifestations of chronic rejection following lung transplantation. We have evaluated the effects of intraperitoneal administration of pioglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, on LB in mice tracheal transplant model. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Animals were divided into three groups (n = 8), isograft (IG) and allograft with (AGP) or without (AGN) pioglitazone. Occlusion rate (OR) of transplanted trachea, CD3, FoxP3 positive cell infiltration, and cytokine levels in the transplanted grafts were analyzed at day 7. In the AGP group, OR was significantly lower than in the AGN group (p <.01). An average of 305 ± 56, and 317 ± 84 CD3-positive T-cells/section was shown in the AGN and AGP groups, respectively (p =.761). Interestingly, an average of 24 ± 18, and 88 ± 28 FoxP3-positive regulatory T-cells (Tregs)/section was shown in AGN and AGP groups, respectively (p =.001). FoxP3 and IL-4 mRNA expression was significantly higher in the AGP group. Pioglitazone can suppress the luminal occlusions of the tracheal graft in an allograft through enhanced Treg infiltration, and may provide new therapies to prevent BO.

KW - Bronchiolitis obliterans

KW - Lung transplantation

KW - Rejection

UR - http://www.scopus.com/inward/record.url?scp=85058704898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058704898&partnerID=8YFLogxK

U2 - 10.1016/j.trim.2018.12.002

DO - 10.1016/j.trim.2018.12.002

M3 - Article

C2 - 30543859

AN - SCOPUS:85058704898

JO - Transplant Immunology

JF - Transplant Immunology

SN - 0966-3274

ER -