Abstract
The initiation and maintenance of airway immune responses in Th2 type allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs). The cytokine microenvironment, produced by local cells, influences the recruitment of specific subsets of immature DCs and their subsequent maturation. In the airway, DCs reside in close proximity to airway epithelial cells (AECs). We examined the ability of primary culture human bronchial epithelial cells (HBECs) to synthesize and secrete the recently described CC-chemokine, MIP-3alpha/CCL20. MIP-3alpha/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3alpha/CCL20 induces selective migration of DCs because CCR6 is expressed on some immature DCs but not on CD14+ DC precursors or mature DCs. HBECs were stimulated with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells were also exposed to small size-fractions of ambient particulate matter. Each of these stimuli induced MIP-3alpha/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in HBECs. Inhibition of the ERK1/2 pathway or p38 reduced cytokine-induced MIP-3alpha/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Air Pollutants / adverse effects*
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Bronchi / cytology*
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Bronchi / drug effects
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Bronchi / immunology*
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Cells, Cultured
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Chemokine CCL20
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Chemokines, CC / genetics
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Chemokines, CC / immunology
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Chemokines, CC / metabolism*
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Cytokines / pharmacology*
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Dendritic Cells / cytology
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Dendritic Cells / metabolism
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Enzyme Inhibitors / pharmacology
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Epithelial Cells / drug effects
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Epithelial Cells / immunology
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Epithelial Cells / metabolism*
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Flavonoids / pharmacology
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Humans
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Imidazoles / pharmacology
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MAP Kinase Signaling System
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology
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Macrophage Inflammatory Proteins / metabolism*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / drug effects
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / metabolism
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Particle Size
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Pyridines / pharmacology
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RNA, Messenger / metabolism
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Receptors, CCR6
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Receptors, Chemokine / metabolism
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Respiratory Mucosa / cytology
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Respiratory Mucosa / immunology
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Respiratory Mucosa / metabolism
Substances
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Air Pollutants
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CCL20 protein, human
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CCR6 protein, human
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Chemokine CCL20
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Chemokines, CC
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Cytokines
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Macrophage Inflammatory Proteins
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Pyridines
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RNA, Messenger
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Receptors, CCR6
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Receptors, Chemokine
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one