NDLI: IL-18BP Improves Early Graft Function and Survival in Lewis-Brown Norway Rat Orthotopic Liver Transplantation Model.

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IL-18BP Improves Early Graft Function and Survival in Lewis-Brown Norway Rat Orthotopic Liver Transplantation Model.

Content Provider	Europe PMC
Author	Meng, Qiang Wu, Weikang Zhang, Wenjie Yuan, Juzheng Yang, Long Zhang, Xuan Tao, Kaishan
Editor	Osna, Natalia
Copyright Year	2022
Abstract	Interleukin-18 (IL-18) can effectively activate natural killer (NK) cells and induce large concentrations of interferon-γ (IFN-γ). In healthy humans, IL-18 binding protein (IL-18BP) can inhibit the binding of IL-18 to IL-18R and counteract the biological action of IL-18 due to its high concentration and high affinity, thus preventing the production of IFN-γ and inhibiting NK-cell activation. Through previous studies and the phenomena observed by our group in pig–non-human primates (NHPs) liver transplantation experiments, we proposed that the imbalance in IL-18/IL-18BP expression upon transplantation encourages the activation, proliferation, and cytotoxic effects of NK cells, ultimately causing acute vascular rejection of the graft. In this research, we used Lewis–Brown Norway rat orthotopic liver transplantation (OLTx) as a model of acute vascular rejection. AAV8-Il18bp viral vectors as gene delivery vehicles were constructed for gene therapy to overexpress IL-18BP and alleviate NK-cell rejection of the graft after transplantation. The results showed that livers overexpressing IL-18BP had reduced damage and could function longer after transplantation, effectively improving the survival time of the recipients.
Journal	Biomolecules
Volume Number	12
PubMed Central reference number	PMC9775331
Issue Number	12
PubMed reference number	36551229
e-ISSN	2218273X
DOI	10.3390/biom12121801
Language	English
Publisher	MDPI
Publisher Date	2022-12-01
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2022 by the authors.
Subject Keyword	orthotopic liver transplantation liver xenotransplantation IL-18 binding protein acute vascular rejection natural killer cell
Content Type	Text
Resource Type	Article
Subject	Biochemistry Molecular Biology

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