Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study

Abstract

The aim of this study was to examine the role of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-8 expression in tumour necrosis factor (TNF)-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells. To this end, the phosphorylation and activation of p38 MAP kinase and the effect of SB 203580, a specific inhibitor of p38 MAP kinase activity, on p38 MAP kinase activity and IL-8 expression in TNF-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells were examined. TNF-alpha- and IL-1alpha- induced phosphorylation and activation of p38 MAP kinase and IL-8 expression in human pulmonary endothelial cells. Inhibition of TNF-alpha- and IL-1alpha-induced p38 MAP kinase activity by SB 203580 inhibited TNF-alpha- and IL-1alpha-induced IL-8 protein production as well as IL-8 messenger ribonucleic acid (mRNA) expression, indicating that SB 203580 was effective at the transcriptional level. These results indicate that p38 mitogen-activated protein kinase plays an important role in the tumour necrosis factor-alpha- and interleukin-1alpha-activated signalling pathway which regulates interleukin-8 expression in human pulmonary vascular endothelial cells.