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A novel MyD88 inhibitor attenuates allograft rejection after heterotopic tracheal transplantation in mice.
- Source :
-
Transplant Immunology . Apr2019, Vol. 53, p1-6. 6p. - Publication Year :
- 2019
-
Abstract
- Abstract 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09663274
- Volume :
- 53
- Database :
- Academic Search Index
- Journal :
- Transplant Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 135183558
- Full Text :
- https://doi.org/10.1016/j.trim.2018.11.006