Transplant immunology · 2018
A novel MyD88 inhibitor attenuates allograft rejection after heterotopic tracheal transplantation in mice.
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Yang Min, Chen Gen, Zhang Xue, Ding Zuochuan, Miao Yan, Yang Yang, Chen Zhonghua Klaus, Jiang Fengchao, Chang Sheng, Zhou Ping
Аннотация
BACKGROUND: After lung transplantation, the major complication limiting the long-term survival of allografts is obliterative bronchiolitis (OB), characterized by chronic rejection. Innate immune responses contribute to the development of OB. In this study, we used a murine heterotopic tracheal transplantation mouse model to examine the effects of a newtype of innate immune inhibitor, TJ-M2010-5.
METHODS: Syngeneic tracheal grafts were transplanted heterotopically from C57BL/6 mice to C57BL/6 mice. Allografts from BALB/c mice were transplanted to C57BL/6 mice. The allograft recipients were treated with TJ-M2010-5, and anti-mouse CD154 (MR-1). The grafts were harvested at 7, 14, and 28 days and evaluated by histological and real-time RT-PCR analyses.
RESULTS: In untreated allografts, almost all epithelial cells fell off at 7 days and tracheal occlusion reached a peak at 28 days. However, the loss of the epithelium and airway obstruction were significantly improved in mice treated with TJ-M2010-5 combined with MR-1. The relative mRNA expression levels of pro-inflammatory cytokines were upregulated in allogeneic tracheal grafts, and treatment with the two drugs reduced the production of pro-inflammatory cytokines and infiltration of inflammatory cells.
CONCLUSIONS: In heterotopic tracheal transplantation models, TJ-M2010-5 combined with MR-1 could ameliorate the development of OB.
METHODS: Syngeneic tracheal grafts were transplanted heterotopically from C57BL/6 mice to C57BL/6 mice. Allografts from BALB/c mice were transplanted to C57BL/6 mice. The allograft recipients were treated with TJ-M2010-5, and anti-mouse CD154 (MR-1). The grafts were harvested at 7, 14, and 28 days and evaluated by histological and real-time RT-PCR analyses.
RESULTS: In untreated allografts, almost all epithelial cells fell off at 7 days and tracheal occlusion reached a peak at 28 days. However, the loss of the epithelium and airway obstruction were significantly improved in mice treated with TJ-M2010-5 combined with MR-1. The relative mRNA expression levels of pro-inflammatory cytokines were upregulated in allogeneic tracheal grafts, and treatment with the two drugs reduced the production of pro-inflammatory cytokines and infiltration of inflammatory cells.
CONCLUSIONS: In heterotopic tracheal transplantation models, TJ-M2010-5 combined with MR-1 could ameliorate the development of OB.
Предметные рубрики MeSH
AnimalsAntibodies, MonoclonalBronchiolitis ObliteransCD40 LigandCytokinesDisease Models, AnimalDrug Therapy, CombinationGraft RejectionHumansImmunologic FactorsInflammation MediatorsLung TransplantationMiceMice, Inbred BALB CMice, Inbred C57BLMyeloid Differentiation Factor 88PiperazinesThiazolesTracheaTransplantation, HeterotopicTransplantation, Homologous