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Vehicular exhaust particles promote allergic airway inflammation through an aryl hydrocarbon receptor-notch signaling cascade.

AbstractBACKGROUND:
Traffic-related particulate matter (PM) has been linked to a heightened incidence of asthma and allergic diseases. However, the molecular mechanisms by which PM exposure promotes allergic diseases remain elusive.
OBJECTIVE:
We sought to determine the expression, function, and regulation of pathways involved in promotion of allergic airway inflammation by PM.
METHODS:
We used gene expression transcriptional profiling, in vitro culture assays, and in vivo murine models of allergic airway inflammation.
RESULTS:
We identified components of the Notch pathway, most notably Jagged 1 (Jag1), as targets of PM induction in human monocytes and murine dendritic cells. PM, especially ultrafine particles, upregulated TH cytokine levels, IgE production, and allergic airway inflammation in mice in a Jag1- and Notch-dependent manner, especially in the context of the proasthmatic IL-4 receptor allele Il4raR576. PM-induced Jag1 expression was mediated by the aryl hydrocarbon receptor (AhR), which bound to and activated AhR response elements in the Jag1 promoter. Pharmacologic antagonism of AhR or its lineage-specific deletion in CD11c(+) cells abrogated the augmentation of airway inflammation by PM.
CONCLUSION:
PM activates an AhR-Jag1-Notch cascade to promote allergic airway inflammation in concert with proasthmatic alleles.
AuthorsMingcan Xia, Loida Viera-Hutchins, Maria Garcia-Lloret, Magali Noval Rivas, Petra Wise, Sean A McGhee, Zena K Chatila, Nancy Daher, Constantinos Sioutas, Talal A Chatila
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 136 Issue 2 Pg. 441-53 (Aug 2015) ISSN: 1097-6825 [Electronic] United States
PMID25825216 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Allergens
  • CD11c Antigen
  • Calcium-Binding Proteins
  • Il4ra protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH1 protein, human
  • Particulate Matter
  • Receptor, Notch1
  • Receptors, Aryl Hydrocarbon
  • Receptors, Cell Surface
  • Serrate-Jagged Proteins
  • Vehicle Emissions
  • Immunoglobulin E
Topics
  • Alleles
  • Allergens (adverse effects)
  • Animals
  • Bronchial Hyperreactivity (chemically induced, genetics, immunology, pathology)
  • CD11c Antigen (genetics, immunology)
  • Calcium-Binding Proteins (genetics, immunology)
  • Dendritic Cells (immunology, pathology)
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin E (genetics)
  • Intercellular Signaling Peptides and Proteins (genetics, immunology)
  • Jagged-1 Protein
  • Membrane Proteins (genetics, immunology)
  • Mice
  • Mice, Transgenic
  • Monocytes (immunology, pathology)
  • Particulate Matter (adverse effects)
  • Primary Cell Culture
  • Receptor, Notch1 (genetics, immunology)
  • Receptors, Aryl Hydrocarbon (genetics, immunology)
  • Receptors, Cell Surface (genetics, immunology)
  • Respiratory Hypersensitivity (chemically induced, genetics, immunology, pathology)
  • Serrate-Jagged Proteins
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer (immunology, pathology)
  • Vehicle Emissions

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