S. Hashimoto et al., p38 mitogen-activated protein kinase regulates IL-8 expression in human pulmonary vascular endothelial cells, EUR RESP J, 13(6), 1999, pp. 1357-1364
The aim of this study was to examine the role of p38 mitogen-activated prot
ein (MAP) kinase in interleukin (IL)-8 expression in tumour necrosis factor
(TNF)-alpha- and IL-1 alpha-stimulated human pulmonary vascular endothelia
l cells.
To this end, the phosphorylation and activation of p38 MAP kinase and the e
ffect of SE 203580, a specific inhibitor of p38 MAP kinase activity, on p38
MAP kinase activity and IL-8 expression in TNF-alpha- and IL-1 alpha-stimu
lated human pulmonary vascular endothelial cells were examined.
TNF-alpha- and IL-1 alpha- induced phosphorylation and activation of p38 MA
P kinase and IL-8 expression in human pulmonary endothelial cells. Inhibiti
on of TNF-alpha- and IL-1 alpha-induced p38 MAP kinase activity by SE 20358
0 inhibited TNF-alpha- and IL-1 alpha-induced IL-8 protein production as we
ll as IL-8 messenger ribonucleic acid (mRNA) expression, indicating that SE
203580 was effective at the transcriptional level.
These results indicate that p38 mitogen-activated protein kinase plays an i
mportant role in the tumour necrosis factor-alpha- and interleukin-1 or-act
ivated signalling pathway which regulates interleukin-8 expression in human
pulmonary vascular endothelial cells.