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Effects of Adenovirus-Mediated Overexpression of JAZF1 on Chronic Inflammation: An In Vitro and In Vivo Study

Fanping Meng, Po Hao, Hongxin Du, Zheng Zhou

Gene Diagnostics Center of Medical Laboratory, Chongqing Three Gorges Central Hospital, Chongqing, China (mainland)

Med Sci Monit Basic Res 2020; 26:e924124

DOI: 10.12659/MSMBR.924124

Available online: 2020-07-13

Published: 2020-07-13


BACKGROUND: Insulin sensitivity and inflammation can be affected by juxtaposition with another zinc finger gene 1 (JAZF1), but its precise role in chronic inflammation is unclear. In this study, JAZF1-overexpression adenovirus plasmids were transfected into macrophages, CD4⁺ T cells, and C57BL/6J mice to assess the role of JAZF1 in chronic inflammation.
MATERIAL AND METHODS: JAZF1 was cloned into an adenovirus skeleton plasmid and transfected in HEK293 cells to package and enrich the virus particles. In vitro, the JAZF1 overexpression adenovirus vector (PAD-JAZF1) was cultured with peritoneal macrophages and peripheral blood CD4⁺ T cells of C57BL/6J mice, and samples were evaluated using flow cytometry. In vivo, PAD-JAZF1 was introduced into C57BL/6J mice, and livers were collected to evaluate factors related to inflammation by hematoxylin & eosin and immunohistochemical staining.
RESULTS: In vitro, PAD-JAZF1 decreased total macrophages, CD11c⁺ macrophages, and the secretion of proinflammatory cytokines, but increased CD206⁺ macrophages. It also decreased total CD4⁺T cells, active T cells, memory T cells, and the secretion of IL-6, IL-10, and IFN-γ, but increased Treg cells and restrictive T cells. In vivo, compared to those in the control group transfected with the adenovirus skeleton vector, mice transfected with the PAD-JAZF1 recombinant adenovirus had fewer CD11c⁺ ATMs and CD4⁺ T cells, lower levels of TNF-alpha and IL-6, and higher IL-10 concentrations in the liver.
CONCLUSIONS: These findings indicate that JAZF1 limits chronic inflammation by reducing macrophage and CD4⁺T cell populations, altering subtype differentiation, and regulating the secretion of immune-related factors.

Keywords: Adenoviridae, Genes, vif, Macrophages, Natural Killer T-Cells