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Ritter, M.* ; Straubinger, K.* ; Schmidt, S.* ; Busch, D.H. ; Hagner, S.* ; Garn, H.* ; da Costa, C.P.* ; Layland, L.E.*

Functional relevance of NLRP3 inflammasome-mediated interleukin (IL)-1 beta during acute allergic airway inflammation.

Clin. Exp. Immunol. 178, 212-223 (2014)
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Overall asthmatic symptoms can be controlled with diverse therapeutic agents. However, certain symptomatic individuals remain at risk for serious morbidity and mortality, which prompts the identification of novel therapeutic targets and treatment strategies. Thus, using an adjuvant-free T helper type 2 (Th2) murine model, we have deciphered the role of interleukin (IL)-1 signalling during allergic airway inflammation (AAI). Because functional IL-1 beta depends on inflammasome activation we first studied asthmatic manifestations in specific inflammasome-deficient [NACHT, LRR and PYD domains-containing protein 3 (NLRP3(-/-)) and apoptosis-associated specklike protein containing a caspase recruitment domain (ASC(-/-))] and IL-1 receptor type 1(-/-) (IL-1R1(-/-)) mice on the BALB/c background. To verify the onset of disease we assessed cellular infiltration in the bronchial regions, lung pathology, airway hyperresponsiveness and ovalbumin (OVA)-specific immune responses. In the absence of NLRP3 inflammasome-mediated IL-1 beta release all symptoms of AAI were reduced, except OVA-specific immunoglobulin levels. To address whether manipulating IL-1 signalling reduced asthmatic development, we administered the IL-1R antagonist anakinra (Kineret (R)) during critical immunological time-points: sensitization or challenge. Amelioration of asthmatic symptoms was only observed when anakinra was administered during OVA challenge. Our findings indicate that blocking IL-1 signalling could be a potential complementary therapy for allergic airway inflammation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Allergy ; Anakinra ; Il-1 Receptor Antagonist ; Il-1 Beta ; Nlrp3-inflammasome; Adaptive Immune-responses; Nalp3 Inflammasome; Receptor Antagonist; Lung Inflammation; Extracellular Atp; Family-members; Induced Asthma; T-cells; Mice; Model
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 0009-9104
e-ISSN 1365-2249
Journal Clinical & Experimental Immunology
Quellenangaben Volume: 178, Issue: 2, Pages: 212-223 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501790-003
DOI 10.1111/cei.12400
WOS ID WOS:000342915800002
Erfassungsdatum 2014-11-10
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