IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases

1 Recent data indicate that interleukin (IL)-17 may contribute to neutrophi lic airway inflammation by inducing the release of neutrophil-mobilizing cy tokines from airway cells. The aim of this study was to evaluate the role o f 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 (in hibitor of p38 MAP kinase), PD98059 (inhibitor of extracellular-signal-regu lated kinase [ERK] pathway), Ro-31-7549 (protein kinase C [PKC] inhibitor), LY 294002 (a phosphatidylinositol 3-kinase [PI 3-kinase] inhibitor) or veh icle. 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 o r IL-8 release in bronchial epithelial cells. 5 Taken together, these data indicate a role for p38 and ERK kinase pathway s in IL-17-induced release of neutrophil-mobilizing cytokines in human bron chial epithelial cells. These mechanisms constitute potential pharmacothera peutical targets for inhibition of the IL-17-mediated airway neutrophilia.