title: IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases.
abstract: 1. Recent data indicate that interleukin (IL)-17 may contribute to neutrophilic airway inflammation by inducing the release of neutrophil-mobilizing cytokines from airway cells. The aim of this study was to evaluate the role of mitogen activated protein kinases in IL-17 induced release of IL-8 and IL-6 in bronchial epithelial cells. 2. Transformed human bronchial epithelial cells (16HBE) were stimulated with either IL-17 or vehicle. Both groups were treated either with SB202190 (inhibitor of p38 MAP kinase), PD98059 (inhibitor of extracellular-signal-regulated kinase [ERK] pathway), Ro-31-7549 (protein kinase C [PKC] inhibitor), LY 294002 (a phosphatidylinositol 3-kinase [PI 3-kinase] inhibitor) or vehicle. IL-6 and IL-8 levels were measured in conditioned media by ELISA. 3. The IL-17-induced release of IL-6 and IL-8 was concentration-dependently inhibited by SB202190 and by PD98059 in bronchial epithelial cells without affecting cell proliferation or survival. 4. Ro-31-7549 and LY294002 had no significant effect on IL-17-induced IL-6 or IL-8 release in bronchial epithelial cells. 4. Taken together, these data indicate a role for p38 and ERK kinase pathways in IL-17-induced release of neutrophil-mobilizing cytokines in human bronchial epithelial cells. These mechanisms constitute potential pharmacotherapeutical targets for inhibition of the IL-17-mediated airway neutrophilia.
authors.affiliation: Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. martii.laan@hjl.gu.se
authors.forename: M
authors.initials: M
authors.lastname: Laan
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: A
authors.initials: A
authors.lastname: Lindén
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C482125:MAP2K1 protein, human