Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase

The changes in airway osmolarity have been described to contribute to the p roduction of exercise-induced bronchoconstriction (EIB) and the development of the late-phase response (LPR). The mechanism has been investigated; how ever, the responsiveness of bronchial epithelial cells (BEC) to hyperosmola rity and the intracellular signals leading to cell activation have not been determined. In this study, we examined the effect of hyperosmolar medium o n interleukin-8 (IL-8) expression and the role of p38 mitogen-activated pro tein (MAP) kinase and c-Jun NH2 terminal kinase (JNK) in human BEC in this response in order to clarify the intracellular signals regulating IL-8 expr ession in hyperosmolarity-stimulated BEG. The results showed that hyperosmo larity induced IL-8 expression in a concentration dependent manner, p38 MAP kinase phosphorylation and activation, and JNK activation whether NaCl or mannitol was used as the solute. SE 203580 as the specific p38 MAP kinase i nhibitor inhibited hyperosmolarity-induced p38 MAP kinase activation and pa rtially inhibited hyperosmolarity-induced IL-8 expression. These results in dicate that p38 MAP kinase, at least in part, regulates hyperosmolarity-ind uced IL-8 expression in BEG. However, other signals such as JNK are possibl y also involved. These results provide new evidence on the mechanism respon sible for the development of the LPR induced by EIB, and a strategy for tre atment with the specific p38 MAP kinase inhibitor.