title: IκB kinase 2 is essential for IgE-induced mast cell de novo cytokine production but not for degranulation.
abstract: 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.
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Peschke
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Weitzmann
authors.affiliation: Department of Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81737 München, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Heger
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Rayk
authors.initials: R
authors.lastname: Behrendt
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Schubert
authors.affiliation: Quintiles, GmbH, 63263 Neu-Isenburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Scholten
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.affiliation: Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Hartmann
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Dudeck
authors.affiliation: Department of Hematology and Oncology, Klinikum rechts der Isar, Technische Universität München, 81737 München, Germany. Electronic address: supprian@lrz.tum.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany. Electronic address: axel.roers@tu-dresden.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
mesh_terms: D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000378:metabolism; D000818:Animals; D015550:Cell Degranulation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C107017:Snap23 protein, mouse; D007073:Immunoglobulin E; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse