Document Detail


The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses.
MedLine Citation:
PMID:  21357533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y(2) receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma.
Authors:
Hideaki Kouzaki; Koji Iijima; Takao Kobayashi; Scott M O'Grady; Hirohito Kita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-25
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-22     Completed Date:  2011-06-16     Revised Date:  2012-04-04    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4375-87     Citation Subset:  AIM; IM    
Affiliation:
Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / physiology,  secretion*
Air Pollutants / immunology*
Allergens / administration & dosage,  physiology*
Alternaria / immunology
Animals
Antigens, Fungal / administration & dosage,  immunology
Cell Line
Coculture Techniques
Extracellular Space / immunology*,  metabolism,  microbiology
Female
Homeostasis / immunology
Humans
Immunity, Innate*
Interleukins / physiology,  secretion*
Mice
Mice, 129 Strain
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Respiratory Mucosa / immunology*,  microbiology,  secretion
Th2 Cells / immunology*,  metabolism,  microbiology
Grant Support
ID/Acronym/Agency:
AI34486/AI/NIAID NIH HHS; AI49235/AI/NIAID NIH HHS; DK074010/DK/NIDDK NIH HHS; HL095811/HL/NHLBI NIH HHS; R01 AI034486-15/AI/NIAID NIH HHS; R01 AI049235-04/AI/NIAID NIH HHS; R01 AI071106-04/AI/NIAID NIH HHS; R21 HL095811-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Air Pollutants; 0/Allergens; 0/Antigens, Fungal; 0/Interleukins; 0/interleukin-33, mouse; 56-65-5/Adenosine Triphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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