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
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP26462134 .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/4
Y1 - 2019/4
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
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U2 - 10.1016/j.trim.2018.12.002
DO - 10.1016/j.trim.2018.12.002
M3 - Article
C2 - 30543859
AN - SCOPUS:85058704898
SN - 0966-3274
VL - 53
SP - 21
EP - 27
JO - Transplant Immunology
JF - Transplant Immunology
ER -