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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1443704

The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells

Provisionally accepted
Remo Poto Remo Poto 1,2,3Leonardo Cristinziano Leonardo Cristinziano 1,3,4Gjada Criscuolo Gjada Criscuolo 1,3,4Caterina Strisciuglio Caterina Strisciuglio 5Francesco Palestra Francesco Palestra 1,3Gianluca Lagnese Gianluca Lagnese 1,3Antonio Di Salvatore Antonio Di Salvatore 1,3Gianni Marone Gianni Marone 1,3,4,6Giuseppe Spadaro Giuseppe Spadaro 1,3,4Stefania Loffredo Stefania Loffredo 1,3,4,6Gilda Varricchi Gilda Varricchi 1,3,4,6*
  • 1 Department of Translational Medical Sciences, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
  • 2 Department of Oncology and Molecular Medicine, National Institute of Health (ISS), Rome, Lazio, Italy
  • 3 WAO Center of Excellence, 80131 Naples, Italy., Naples, Campania, Italy
  • 4 Interdepartmental Research Center in Basic and Clinical Immunological Sciences, University of Naples Federico II, Naples, Campania, Italy
  • 5 University of Campania Luigi Vanvitelli, Caserta, Campania, Italy
  • 6 Institute for Endocrinology and Experimental Oncology Gaetano Salvatore, Department of Biomedical Sciences, National Research Council (CNR), Naples, Campania, Italy

The final, formatted version of the article will be published soon.

    The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils. In this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE-and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs).Ruxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C 4 ) from human basophils. Ruxolitinib also inhibited anti-IgE-and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs. These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.

    Keywords: Asthma, basophil, Histamine, IL-4, IL-13, mast cell, Polycythemia Vera, Ruxolitinib

    Received: 04 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Poto, Cristinziano, Criscuolo, Strisciuglio, Palestra, Lagnese, Di Salvatore, Marone, Spadaro, Loffredo and Varricchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Gilda Varricchi, Department of Translational Medical Sciences, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy

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