IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation
The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IκB kinase 2 (IKK2) was reported to couple IgE-induced signals to MC degranulation by phosphorylating the SNARE protein SNAP23. We investigated MC responses in mice with MC-specif...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714006305 |
| _version_ | 1818156059820294144 |
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| author | Katrin Peschke Anke Weitzmann Klaus Heger Rayk Behrendt Nadja Schubert Julia Scholten David Voehringer Karin Hartmann Anne Dudeck Marc Schmidt-Supprian Axel Roers |
| author_facet | Katrin Peschke Anke Weitzmann Klaus Heger Rayk Behrendt Nadja Schubert Julia Scholten David Voehringer Karin Hartmann Anne Dudeck Marc Schmidt-Supprian Axel Roers |
| author_sort | Katrin Peschke |
| collection | DOAJ |
| description | The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IκB kinase 2 (IKK2) was reported to couple IgE-induced signals to MC degranulation by phosphorylating the SNARE protein SNAP23. We investigated MC responses in mice with MC-specific inactivation of IKK2 or NF-κB essential modulator (NEMO), or animals with MC-specific expression of a mutant, constitutively active IKK2. We show that the IgE-induced late-phase cytokine response is reduced in mice lacking IKK2 or NEMO in MCs. However, anaphylactic in vivo responses of these animals are not different from those of control mice, and in vitro IKK2-deficient MCs readily phosphorylate SNAP23 and degranulate similarly to control cells in response to allergen or calcium ionophore. Constitutive overactivation of the NF-κB pathway has only slight effects on allergen-triggered MC responses. Thus, IKK2 is dispensable for MC degranulation, and the important question how IgE-induced signals trigger MC vesicle fusion remains open. |
| first_indexed | 2024-12-11T14:52:17Z |
| format | Article |
| id | doaj.art-019cb843764749389bb6becf3a0e6cb1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T14:52:17Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-019cb843764749389bb6becf3a0e6cb12022-12-22T01:01:25ZengElsevierCell Reports2211-12472014-09-01851300130710.1016/j.celrep.2014.07.046IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for DegranulationKatrin Peschke0Anke Weitzmann1Klaus Heger2Rayk Behrendt3Nadja Schubert4Julia Scholten5David Voehringer6Karin Hartmann7Anne Dudeck8Marc Schmidt-Supprian9Axel Roers10Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyInstitute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyDepartment of Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81737 München, GermanyInstitute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyInstitute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyQuintiles, GmbH, 63263 Neu-Isenburg, GermanyDepartment of Infection Biology, Universitätsklinikum Erlangen, 91054 Erlangen, GermanyDepartment of Dermatology, University of Cologne, 50937 Cologne, GermanyInstitute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyDepartment of Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81737 München, GermanyInstitute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, GermanyThe immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IκB kinase 2 (IKK2) was reported to couple IgE-induced signals to MC degranulation by phosphorylating the SNARE protein SNAP23. We investigated MC responses in mice with MC-specific inactivation of IKK2 or NF-κB essential modulator (NEMO), or animals with MC-specific expression of a mutant, constitutively active IKK2. We show that the IgE-induced late-phase cytokine response is reduced in mice lacking IKK2 or NEMO in MCs. However, anaphylactic in vivo responses of these animals are not different from those of control mice, and in vitro IKK2-deficient MCs readily phosphorylate SNAP23 and degranulate similarly to control cells in response to allergen or calcium ionophore. Constitutive overactivation of the NF-κB pathway has only slight effects on allergen-triggered MC responses. Thus, IKK2 is dispensable for MC degranulation, and the important question how IgE-induced signals trigger MC vesicle fusion remains open.http://www.sciencedirect.com/science/article/pii/S2211124714006305 |
| spellingShingle | Katrin Peschke Anke Weitzmann Klaus Heger Rayk Behrendt Nadja Schubert Julia Scholten David Voehringer Karin Hartmann Anne Dudeck Marc Schmidt-Supprian Axel Roers IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation Cell Reports |
| title | IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation |
| title_full | IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation |
| title_fullStr | IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation |
| title_full_unstemmed | IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation |
| title_short | IκB Kinase 2 Is Essential for IgE-Induced Mast Cell De Novo Cytokine Production but Not for Degranulation |
| title_sort | iκb kinase 2 is essential for ige induced mast cell de novo cytokine production but not for degranulation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714006305 |
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