Reactive oxygen intermediates are involved in IL-8 production induced by hyperosmotic stress in human bronchial epithelial cells.
Changes in the osmolarity of the airway surface fluid have been described to be involved in the pathogenesis of exercise induced asthma, and are suggested as the major cause of the lung disease in cystic fibrosis. In this study, we examined the signaling pathway of hyperosmotic challenge to interleukin-8 (IL-8). Hyperosmolarity (NaCl) caused a time- and concentration-dependent increase in IL-8 expression and secretion in bronchial epithelial cells. These effects could be blocked by antioxidants, such as DMSO, DMTU, DTT, and beta-mercaptoethanol, suggesting an involvement of reactive oxygen intermediates (ROI) in the signal transduction of hyperosmolarity-induced IL-8 synthesis. Since IL-8 is regulated by MAP kinases, we examined the influence of MAP kinase inhibitors on hyperosmolarity-induced IL-8 expression. The results show that this induction is regulated by p38 MAPK and not by ERK1/2. Furthermore, antioxidants blocked the activation of p38 MAPK induced by hyperosmolarity. These results suggest that ROIs are critical for p38 MAPK mediated IL-8 expression by hyperosmolarity.
Loitsch
S M
SM
Department of Internal Medicine, Department of Dermatology, Institute of Pharmaceutical Chemistry, University of Frankfurt, Theodor Stern Kai 7, Frankfurt, 60590, Germany.
von Mallinckrodt
C
C
Kippenberger
S
S
Steinhilber
D
D
Wagner
T O
TO
Bargon
J
J
D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases