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

Background 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...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2015-08, Vol.136 (2), p.441-453
Main Authors: Xia, Mingcan, PhD, Viera-Hutchins, Loida, MD, Garcia-Lloret, Maria, MD, Noval Rivas, Magali, PhD, Wise, Petra, PhD, McGhee, Sean A., MD, Chatila, Zena K, Daher, Nancy, PhD, Sioutas, Constantinos, PhD, Chatila, Talal A., MD, MSc
Format: Article
Language:English
Subjects:
airway hyperresponsiveness
Alleles
Allergens - adverse effects
allergic airway inflammation
Allergy and Immunology
Animals
Antigens
Aqueous solutions
aryl hydrocarbon receptor
Asthma
Atherosclerosis
Atoms & subatomic particles
Bronchial Hyperreactivity - chemically induced
Bronchial Hyperreactivity - genetics
Bronchial Hyperreactivity - immunology
Bronchial Hyperreactivity - pathology
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - immunology
CD11c Antigen - genetics
CD11c Antigen - immunology
Cytokines
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - pathology
diesel exhaust particles
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation
Humans
Hydrocarbons
Immunoglobulin E - genetics
Inflammation
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - immunology
Jagged 1
Jagged-1 Protein
Lymphocytes
Membrane Proteins - genetics
Membrane Proteins - immunology
Mice
Mice, Transgenic
Monocytes - immunology
Monocytes - pathology
Notch
Particulate Matter - adverse effects
Pollutants
Primary Cell Culture
Receptor, Notch1 - genetics
Receptor, Notch1 - immunology
Receptors, Aryl Hydrocarbon - genetics
Receptors, Aryl Hydrocarbon - immunology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Respiratory Hypersensitivity - chemically induced
Respiratory Hypersensitivity - genetics
Respiratory Hypersensitivity - immunology
Respiratory Hypersensitivity - pathology
Serrate-Jagged Proteins
Signal Transduction
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Helper-Inducer - pathology
Traffic
Traffic-related particulate matter
ultrafine particles
Vehicle Emissions
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Summary:Background 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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2015.02.014