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p38 Mitogen-activated protein kinase regulates IL‐8 expression in human pulmonary vascular endothelial cells

1999; European Respiratory Society; Volume: 13; Issue: 6 Linguagem: Inglês

10.1034/j.1399-3003.1999.13f21.x

1399-3003

Shu Hashimoto, Ken Matsumoto, Yasuhiro Gon, Shuichiro Maruoka, Ikuko Takeshita, Shinichi Hayashi, Toshiya Koura, Kosei Kujime, Takashi Horie,

interferon and immune responses

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.