Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening.
Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening.
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通过代谢相关化合物库筛选鉴定甲磺酸萘莫司他作为 NK 细胞 IFNγ 产生的选择性刺激剂
DOI：
10.1007/s12026-022-09266-z
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发表时间：
2022-06
影响因子：
4.4
通讯作者：
Deng Y
中科院分区：
文献类型：
--
作者：
Yang Q;Zhang S;Wu S;Yao B;Wang L;Li Y;Peng H;Huang M;Bi Q;Xiong P;Li L;Deng Y;Deng Y
自然杀伤（NK）细胞在控制病毒感染和恶性细胞方面发挥重要作用。识别能够激活NK细胞的新分子可能有效地提高这些细胞的抗病毒和抗肿瘤活性。在这项研究中，通过使用商业上可获得的代谢相关化合物库，我们通过在与IL-12或IL-15孵育外周血单个核细胞（PBMC）18 h后通过流式细胞术测定干扰素-γ（IFN-γ）+ NK细胞的比率来初步筛选化合物激活NK细胞的能力。我们的数据显示，8种化合物（甲磺酸萘莫司他（NM）、马钱素、氟伐他汀钠、阿托伐他汀钙、洛伐他汀、辛伐他汀、瑞舒伐他汀钙和匹伐他汀钙）和3种化合物（NM、艾司洛尔和辛伐他汀）分别增加了与IL-12和IL-15培养的PBMC中表达IFN-γ的NK细胞和CD 3 + T细胞的比例。当与富集的NK细胞（纯度≥ 80.0%）孵育时，在IL-12或IL-15存在下，仅NM增强NK细胞IFN-γ的产生。当与纯化的NK细胞（纯度≥ 99.0%）孵育时，在存在或不存在IL-18的情况下，NM促进NK细胞IFN-γ分泌。NM对NK细胞的杀伤活性无明显影响。总的来说，我们的研究确定NM作为NK细胞产生IFN-γ的选择性刺激剂，为预防和治疗选定人群中的感染或癌症提供了新的策略。在线版本包含补充材料，可通过10.1007/s12026-022-09266-z获得。
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. The online version contains supplementary material available at 10.1007/s12026-022-09266-z.
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DOI：
10.1084/jem.183.6.2645
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baker MB;Altman NH;Podack ER;Levy RB
通讯作者：
Levy RB
影响因子：
5.6
作者：
Ahmadi, Majid;Ghaebi, Mahnaz;Yousefi, Mehdi
通讯作者：
Yousefi, Mehdi
影响因子：
64.8
作者：
Correia, Ana Luisa;Guimaraes, Joao C.;Bentires-Alj, Mohamed
通讯作者：
Bentires-Alj, Mohamed
影响因子：
32.4
作者：
Glasner A;Levi A;Enk J;Isaacson B;Viukov S;Orlanski S;Scope A;Neuman T;Enk CD;Hanna JH;Sexl V;Jonjic S;Seliger B;Zitvogel L;Mandelboim O
通讯作者：
Mandelboim O
影响因子：
1.6
作者：
Doi S;Akashi YJ;Takita M;Yoshida H;Morikawa D;Ishibashi Y;Higuma T;Fujitani S
通讯作者：
Fujitani S