Abstract
The cytokine interleukin-17 may play a role in the recruitment of airway neutrophils, and interleukin-17 protein is increased in the airways of patients with asthma. In this study, we characterised the effect of interleukin-17 on the release of the neutrophil-recruiting cytokines granulocyte chemotactic protein (GCP)-2, growth-related oncogene (GRO)-alpha and interleukin-8 in human bronchial epithelial (HBE) cells. We also characterised the involvement of mitogen-activated protein (MAP) kinases as well as the effect of beta-adrenoceptor and glucocorticoid receptor stimulation and calcineurin and P-glycoprotein inhibition on these epithelial responses to interleukin-17. We found that interleukin-17 (1-1000 ng/ml) increased the release of GCP-2, GRO-alpha and interleukin-8 in a concentration-dependent manner. This interleukin-17-induced release of C-X-C chemokines was sensitive to inhibition of the p38 MAP kinase pathway and to stimulation of glucocorticoid receptors. In contrast, stimulation of beta-adrenoceptors increased the release of interleukin-8 and did not markedly alter the release of GCP-2 and GRO-alpha. Inhibition of calcineurin and of P-glycoproteins did not exert any substantial effect on the release of C-X-C chemokines. In conclusion, interleukin-17 bears the potential to increase neutrophil recruitment into the airways by releasing several, different C-X-C chemokines, including GCP-2, GRO-alpha and interleukin-8 in human bronchial epithelial cells. Inhibition of the p38 MAP kinase pathway and glucocorticoid receptor stimulation constitute two credible therapeutic strategies against this interleukin-17-induced release of neutrophil-recruiting cytokines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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Adrenergic beta-Agonists / pharmacology
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Albuterol / pharmacology
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Bronchi / cytology
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Bronchi / drug effects*
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Bronchi / metabolism
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Calcineurin Inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Cell Line, Transformed
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Chemokine CXCL1
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Chemokine CXCL6
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Chemokines / metabolism*
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Chemokines, CXC / metabolism
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Chemotactic Factors / metabolism
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Cyclosporine / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Flavonoids / pharmacology
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Humans
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Hydrocortisone / pharmacology
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Imidazoles / pharmacology
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Intercellular Signaling Peptides and Proteins / metabolism
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Interleukin-17 / pharmacology*
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Interleukin-8 / metabolism
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Pyridines / pharmacology
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Receptors, Adrenergic, beta / drug effects
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Receptors, Adrenergic, beta / metabolism
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Receptors, Glucocorticoid / drug effects
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Receptors, Glucocorticoid / metabolism
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p38 Mitogen-Activated Protein Kinases
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Adrenergic beta-Agonists
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CXCL1 protein, human
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CXCL6 protein, human
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Calcineurin Inhibitors
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Chemokine CXCL1
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Chemokine CXCL6
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Chemokines
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Chemokines, CXC
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Chemotactic Factors
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Intercellular Signaling Peptides and Proteins
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Interleukin-17
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Interleukin-8
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Pyridines
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Receptors, Adrenergic, beta
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Receptors, Glucocorticoid
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Cyclosporine
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
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Albuterol
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Hydrocortisone