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IL‐17‐induced cytokine release in human bronchial epithelial cells in vitro : role of mitogen‐activated protein (MAP) kinases
Author(s) -
Laan Martti,
Lötvall Jan,
Chung K Fan,
Lindén Anders
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704063
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , kinase , ly294002 , microbiology and biotechnology , mitogen activated protein kinase , phosphatidylinositol , biology , cytokine , interleukin 8 , interleukin 22 , mitogen activated protein kinase kinase , protein kinase a , immunology , interleukin
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. 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. 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. Ro‐31‐7549 and LY294002 had no significant effect on IL‐17‐induced IL‐6 or IL‐8 release in bronchial epithelial cells. 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.British Journal of Pharmacology (2001) 133 , 200–206; doi: 10.1038/sj.bjp.0704063