Frontiers in Immunology (Aug 2024)
The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells
- Remo Poto,
- Remo Poto,
- Remo Poto,
- Leonardo Cristinziano,
- Leonardo Cristinziano,
- Leonardo Cristinziano,
- Gjada Criscuolo,
- Gjada Criscuolo,
- Gjada Criscuolo,
- Caterina Strisciuglio,
- Francesco Palestra,
- Francesco Palestra,
- Gianluca Lagnese,
- Gianluca Lagnese,
- Antonio Di Salvatore,
- Antonio Di Salvatore,
- Gianni Marone,
- Gianni Marone,
- Gianni Marone,
- Gianni Marone,
- Giuseppe Spadaro,
- Giuseppe Spadaro,
- Giuseppe Spadaro,
- Stefania Loffredo,
- Stefania Loffredo,
- Stefania Loffredo,
- Stefania Loffredo,
- Gilda Varricchi,
- Gilda Varricchi,
- Gilda Varricchi,
- Gilda Varricchi
Affiliations
- Remo Poto
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Remo Poto
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), Rome, Italy
- Remo Poto
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Leonardo Cristinziano
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Leonardo Cristinziano
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Leonardo Cristinziano
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Gjada Criscuolo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Gjada Criscuolo
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Gjada Criscuolo
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Francesco Palestra
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Francesco Palestra
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Gianluca Lagnese
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Gianluca Lagnese
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Antonio Di Salvatore
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Antonio Di Salvatore
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Gianni Marone
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Gianni Marone
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Gianni Marone
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Gianni Marone
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy
- Giuseppe Spadaro
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Giuseppe Spadaro
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Giuseppe Spadaro
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Stefania Loffredo
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Stefania Loffredo
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy
- Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Gilda Varricchi
- World Allergy Organization (WAO) Center of Excellence, Naples, Italy
- Gilda Varricchi
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Gilda Varricchi
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy
- DOI
- https://doi.org/10.3389/fimmu.2024.1443704
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionThe 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.MethodsIn 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).ResultsRuxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) 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.DiscussionThese 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
