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Open Access 15-02-2022 | Statins | Original Article

Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening

Authors: Qinglan Yang, Shuju Zhang, Shuting Wu, Baige Yao, Lili Wang, Yana Li, Hongyan Peng, Minghui Huang, Qinghua Bi, Peiwen Xiong, Liping Li, Yafei Deng, Youcai Deng

Published in: Immunologic Research | Issue 3/2022

Abstract

Natural killer (NK) cells play important roles in controlling virus-infected and malignant cells. The identification of new molecules that can activate NK cells may effectively improve the antiviral and antitumour activities of these cells. In this study, by using a commercially available metabolism-related compound library, we initially screened the capacity of compounds to activate NK cells by determining the ratio of interferon-gamma (IFN-γ)⁺ NK cells by flow cytometry after the incubation of peripheral blood mononuclear cells (PBMCs) with IL-12 or IL-15 for 18 h. Our data showed that eight compounds (nafamostat mesylate (NM), loganin, fluvastatin sodium, atorvastatin calcium, lovastatin, simvastatin, rosuvastatin calcium, and pitavastatin calcium) and three compounds (NM, elesclomol, and simvastatin) increased the proportions of NK cells and CD3⁺ T cells that expressed IFN-γ among PBMCs cultured with IL-12 and IL-15, respectively. When incubated with enriched NK cells (purity ≥ 80.0%), only NM enhanced NK cell IFN-γ production in the presence of IL-12 or IL-15. When incubated with purified NK cells (purity ≥ 99.0%), NM promoted NK cell IFN-γ secretion in the presence or absence of IL-18. However, NM showed no effect on NK cell cytotoxicity. Collectively, our study identifies NM as a selective stimulator of IFN-γ production by NK cells, providing a new strategy for the prevention and treatment of infection or cancer in select populations.

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Title: Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening
Authors: Qinglan Yang
Shuju Zhang
Shuting Wu
Baige Yao
Lili Wang
Yana Li
Hongyan Peng
Minghui Huang
Qinghua Bi
Peiwen Xiong
Liping Li
Yafei Deng
Youcai Deng
Publication date: 15-02-2022
Publisher: Springer US
Keyword: Statins
Published in: Immunologic Research / Issue 3/2022
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-022-09266-z

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Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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