Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism.
Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients. We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry. Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways. These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells.
Wong
C K
CK
Dept of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Cao
J
J
Yin
Y B
YB
Lam
C W K
CW
D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000166:cytology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D018920:Coculture Techniques; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508717:IL17A protein, human; C109985:IL17RA protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D053722:Receptors, Interleukin-17; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases