Details

Autor(en) / Beteiligte

• Zhang, Yan
• Yang, Yu
• Li, Xianduo
• Chen, Dongdong
• Tang, Guanbao
• Men, Tongyi

Titel

Thalidomide ameliorate graft chronic rejection in an allogenic kidney transplant model

Ist Teil von

• International immunopharmacology, 2019-06, Vol.71, p.32-39

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Chronic T cell mediated rejection (TCMR), which is characterized by infiltration of the interstitium by T cells and macrophages, still remains a major barrier to the long-term survival of kidney transplantation. Our recent report indicated that thalidomide can attenuate graft arteriosclerosis in an aortic transplant model. In this study, we investigated the effect of thalidomide on chronic TCMR in a rat model of kidney transplantation. Fischer or Lewis kidney allografts were transplanted into Lewis recipient rats. After kidney transplantation, recipient rats were divided into 3 groups: the isograft (Iso) group, allograft (Allo) group, and thalidomide (Tha) group. Rats were sacrificed at 8 weeks after kidney transplantation, and blood and kidney samples were collected. Serum concentrations of creatinine (SCr),interleukin (IL)-2, IL-6, IL-17, and TNF-α in recipients were determined, and flow cytometry was used to detect the percentages of CD4+CD25+, CD4+ Foxp3+and CD4+Th17+ cell subsets in the peripheral blood. Grafts were procured for histopathological examination, and the expressions of α-SMA, transforming growth-β1 (TGF-β1), and VEGF in kidney grafts were investigated using Western blot. Thalidomide treatment significantly ameliorated chronic rejection, reduced renal allograft tissue damage, and decreased serum creatinine levels. Attenuation of chronic TCMR was due to the prohibited production of inflammatory cytokines, altered distribution of the CD4+ CD25+ FoxP3+ regulatory T (Treg) and CD4+ Th17+ cells in the peripheral blood, and decreased expression of TGF-β1, α-SMA, and VEGF in the kidney graft. These results demonstrated that thalidomide could effectively ameliorate chronic TCMR in a rat kidney transplant model. •Thalidomide ameliorated chronic rejection after kidney transplantation.•Thalidomide ameliorated inflammatory environment after kidney transplantation.•Thalidomide moderates the Th17/Treg balance after kidney transplantation.