p38 Mitogen-activated protein kinase regulates IL-8 expression in human pulmonary vascular endothelial cells.
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.
Hashimoto
S
S
First Dept. of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Matsumoto
K
K
Gon
Y
Y
Maruoka
S
S
Takeshita
I
I
Hayashi
S
S
Koura
T
T
Kujime
K
K
Horie
T
T
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D016209:Interleukin-8; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580