Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation |
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Authors: | Yong Chen PhD Haizhong Liu MD Zuojin Liu PhD Shaoyong Liang PhD Jie Chen MD Feiwu Long MD Yong Peng PhD Lünan Yan PhD Jianping Gong PhD |
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Institution: | aDepartment of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China;bLiver Transplantation Center, West China Hospital, Sichuan University, Chendu, China |
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Abstract: | BackgroundThe role of inducible costimulator (ICOS) in transplantation immunity remains unclear.MethodsA Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-γ and tumor-necrosis factor-α levels were determined.ResultsRecipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-γ and tumor-necrosis factor-α, suppress cell infiltration into grafts, and promote tolerance in the interference group.ConclusionsOur data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect allografts from acute rejection. |
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Keywords: | Acute rejection Inducible costimulator Live transplantation RNA interference T lymphocyte |
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