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 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/metabolism

Bronchi/cytology/*drug effects/enzymology/metabolism

Cell Division/drug effects

Cell Line

Transformed

Cytokines/metabolism/*secretion

Enzyme Inhibitors/pharmacology

Epithelial Cells/cytology/*drug effects/enzymology/metabolism

Humans

Interleukin-17/*pharmacology

Interleukin-6/metabolism/secretion

Interleukin-8/metabolism/secretion

MAP Kinase Kinase 1

MAP Kinase Signaling System/drug effects

inhibitors/metabolism

Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism

Protein Kinase C/antagonists & inhibitors/metabolism

Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism

p38 Mitogen-Activated Protein Kinases

Publikations- och innehållstyp

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art (ämneskategori)