S. Hashimoto et al., Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase, AM J R CRIT, 159(2), 1999, pp. 634-640
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.