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Airway Epithelial Cells Release MIP-3/CCL20 in Response to Cytokines and Ambient Particulate Matter

Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Department of Environmental Medicine, Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York

Address correspondence to: Joan Reibman, M.D., New York University School of Medicine, Division of Pulmonary and Critical Care Medicine, 550 1st Avenue, Room NB7N24, New York, NY 10016. E-mail: reibmj01{at}gcrc.med.nyu.edu

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-3/CCL20. MIP-3/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3/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- and interleukin (IL)-1ß 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-3/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-3/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway.

Abbreviations: airway epithelial cell, AEC • analysis of variance, ANOVA • bronchial epithelial cell growth medium, BEGM • dendritic cell, DC • enzyme-linked immunoabsorbent assay, ELISA • granulocyte-macrophage colony stimulating factor, GM-CSF • human bronchial epithelial cell, HBEC • interleukin, IL • lipopolysaccharide, LPS • mitogen-activated protein kinase, MAPK • macrophage inhibitory protein, MIP • particulate matter, PM • polyvinylidene difluoride, PVDF • reverse transcription polymerase chain reaction, RT-PCR • tumor necrosis factor-, TNF- • ultrafine, UF

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