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nk cell-derived ifn-γ tlr-mediated nf-κb signaling anti-ifn-γ-fitc antibodies ifn-γ-producing nk cells tnf-related apoptosis-inducing ligand sustained ifn-γ production ifn-γ-producing cd3+cd56− enhance ifn-γ production metabolism-related compound library death receptor-related apoptosis prolonged ifn-γ production nk cell-based immunotherapy inducing ifn-γ production hepatic ischemia-reperfusion injury regulate ifn-γ production induce ifn-γ production enhanced ifn-γ secretion enhances ifn-γ production receptor-mediated nf-κb fluorescence-activated cell sorting promote ifn-γ secretion rag-dependent receptor rearrangement induce ifn-γ secretion enzyme-linked immunosorbent assay monocyte-derived cytokine production higher ifn-γ production ifn-γ+ nk cells nuclear factor-κb enhances nk cell-mediated cytotoxicity ifn-gamma gene expression inhibit 3-hydroxy-3-methylglutaryl coenzyme increased ifn-γ secretion anti-cd56-apc antibodies article download pdf fine-tuning cytokine signals donor-derived nk cells increase ifn-γ production assessed ifn-γ secretion enhances anti-tumor activity statin-induced proinflammatory response ifn-γ levels secreted measured ifn-γ secretion ifn-gamma production ~ 200 pg/ml ifn-γ ifn-γ-producing srebp-controlled glucose metabolism graft-versus-host disease natural killer cells killer cell lectin inducing tumour-specific

Questions {❓}

• Interferon-γ: teammate or opponent in the tumour microenvironment?

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WebPage:
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         headline:Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening
         description: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.
         datePublished:2022-02-15T00:00:00Z
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            IFN-γ
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            Medicine/Public Health
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      headline:Identification of nafamostat mesylate as a selective stimulator of NK cell IFN-γ production via metabolism-related compound library screening
      description: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.
      datePublished:2022-02-15T00:00:00Z
      dateModified:2022-02-15T00:00:00Z
      pageStart:354
      pageEnd:364
      license:http://creativecommons.org/licenses/by/4.0/
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      keywords:
         Natural killer cell
         IFN-γ
         Statins
         Nafamostat mesylate
         Immunology
         Allergology
         Medicine/Public Health
         general
         Internal Medicine
      image:
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            address:
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            address:
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            address:
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            address:
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            address:
               name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
               type:PostalAddress
            type:Organization
            name:Hunan Children’s Hospital, University of South China
            address:
               name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
               type:PostalAddress
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      email:[email protected]
      name:Youcai Deng
      url:http://orcid.org/0000-0001-5488-8576
      affiliation:
            name:Army Medical University (Third Military Medical University)
            address:
               name:Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
      name:Pediatric Intensive Care Unit, Hunan Children’s Hospital, University of South China, Changsha, China
      name:Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing, China

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