PMID- 25176657
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20140913
IS  - 2211-1247 (Electronic)
VI  - 8
IP  - 5
DP  - 2014 Sep 11
TI  - IkappaB kinase 2 is essential for IgE-induced mast cell de novo cytokine production 
      but not for degranulation.
PG  - 1300-7
LID - S2211-1247(14)00630-5 [pii]
LID - 10.1016/j.celrep.2014.07.046 [doi]
AB  - The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the 
      pathogenesis of type I allergy and asthma. IkappaB 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-kappaB 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-kappaB 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.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Peschke, Katrin
AU  - Peschke K
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany.
FAU - Weitzmann, Anke
AU  - Weitzmann A
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany.
FAU - Heger, Klaus
AU  - Heger K
AD  - Department of Hematology and Oncology, Klinikum rechts der Isar, Technische 
      Universitat Munchen, 81737 Munchen, Germany.
FAU - Behrendt, Rayk
AU  - Behrendt R
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany.
FAU - Schubert, Nadja
AU  - Schubert N
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany.
FAU - Scholten, Julia
AU  - Scholten J
AD  - Quintiles, GmbH, 63263 Neu-Isenburg, Germany.
FAU - Voehringer, David
AU  - Voehringer D
AD  - Department of Infection Biology, Universitatsklinikum Erlangen, 91054 Erlangen, 
      Germany.
FAU - Hartmann, Karin
AU  - Hartmann K
AD  - Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
FAU - Dudeck, Anne
AU  - Dudeck A
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany.
FAU - Schmidt-Supprian, Marc
AU  - Schmidt-Supprian M
AD  - Department of Hematology and Oncology, Klinikum rechts der Isar, Technische 
      Universitat Munchen, 81737 Munchen, Germany. Electronic address: 
      supprian@lrz.tum.de.
FAU - Roers, Axel
AU  - Roers A
AD  - Institute for Immunology, Technische Universitat Dresden, Medical Faculty Carl 
      Gustav Carus, 01307 Dresden, Germany. Electronic address: 
      axel.roers@tu-dresden.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140828
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Allergens)
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NEMO protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Qb-SNARE Proteins)
RN  - 0 (Qc-SNARE Proteins)
RN  - 0 (Snap23 protein, mouse)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
SB  - IM
MH  - Allergens/immunology
MH  - Anaphylaxis/metabolism
MH  - Animals
MH  - *Cell Degranulation
MH  - Cytokines/genetics/*metabolism
MH  - I-kappa B Kinase/genetics/*metabolism
MH  - Immunoglobulin E/*immunology
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Mast Cells/immunology/*metabolism/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Qb-SNARE Proteins/metabolism
MH  - Qc-SNARE Proteins/metabolism
EDAT- 2014/09/02 06:00
MHDA- 2015/05/29 06:00
CRDT- 2014/09/02 06:00
PHST- 2013/10/07 00:00 [received]
PHST- 2014/06/06 00:00 [revised]
PHST- 2014/07/25 00:00 [accepted]
PHST- 2014/09/02 06:00 [entrez]
PHST- 2014/09/02 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
AID - S2211-1247(14)00630-5 [pii]
AID - 10.1016/j.celrep.2014.07.046 [doi]
PST - ppublish
SO  - Cell Rep. 2014 Sep 11;8(5):1300-7. doi: 10.1016/j.celrep.2014.07.046. Epub 2014 
      Aug 28.