A novel MyD88 inhibitor attenuates allograft rejection after heterotopic tracheal transplantation in mice

Autor: Xue Zhang, Ping Zhou, Fengchao Jiang, Sheng Chang, Zhonghua Klaus Chen, Min Yang, Yan Miao, Yang Yang, Gen Chen, Zuochuan Ding
Rok vydání: 2018
Předmět:
Graft Rejection
Pathology
medicine.medical_specialty
Transplantation
Heterotopic
medicine.medical_treatment
Immunology
CD40 Ligand
Bronchiolitis obliterans
030230 surgery
Piperazines
03 medical and health sciences
Mice
0302 clinical medicine
Immunology and Allergy
Medicine
Lung transplantation
Animals
Humans
Immunologic Factors
Transplantation
Homologous
CD154
Bronchiolitis Obliterans
Transplantation
Mice
Inbred BALB C
Innate immune system
biology
business.industry
Antibodies
Monoclonal
medicine.disease
Epithelium
Mice
Inbred C57BL
Trachea
Disease Models
Animal
Thiazoles
surgical procedures
operative
medicine.anatomical_structure
Myeloid Differentiation Factor 88
biology.protein
Cytokines
Drug Therapy
Combination
Antibody
Inflammation Mediators
business
Infiltration (medical)
030215 immunology
Lung Transplantation
Zdroj: Transplant immunology. 53
ISSN: 1878-5492
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: