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 t o be involved in the pathogenesis of exercise induced asthma, and are sugge sted as the major cause of the lung disease in cystic fibrosis. In this stu dy, we examined the signaling pathway of hyperosmotic challenge to interleu kin-8 (IL-8). Hyperosmolarity (NaCl) caused a time- and concentration-depen dent increase in IL-8 expression and secretion in bronchial epithelial cell s. These effects could be blocked by antioxidants, such as DMSO, DMTU, DTT, and beta-mercaptoethanol, suggesting an involvement of reactive oxygen int ermediates (ROI) in the signal transduction of hyperosmolarity-induced IL-8 synthesis. Since IL-8 is regulated by MAP kinases, we examined the influen ce 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. (C) 2000 Academic Press.