p38 MAP kinase regulates RANTES production by TNF-alpha-stimulated human pulmonary vascular endothelial cells.
BACKGROUND
RANTES plays an important role in the production of allergic inflammation of the airway through its chemotactic activity for eosinophils. However, the intracellular signal regulating RANTES expression in human pulmonary vascular endothelial cells has not been determined. In the present study, therefore, we examined the role of p38 mitogen-activated protein (MAP) kinase in RANTES production by tumor necrosis factor (TNF)-alpha-stimulated pulmonary vascular endothelial cells in order to clarify the signal transduction pathway regulating RANTES production by pulmonary vascular endothelial cells.


METHODS
We examined p38 MAP kinase activation, and the effect of SB 203580, as the specific inhibitor for p38 MAP kinase, on p38 MAP kinase activity and RANTES production by TNF-alpha-stimulated human pulmonary vascular endothelial cells.


RESULTS
The results showed that TNF-alpha induced RANTES production and p38 MAP kinase activity in human pulmonary vascular endothelial cells. Abrogation of p38 MAP kinase activity by SB 203580 repressed TNF-alpha-induced p38 MAP kinase activity and RANTES production.


CONCLUSIONS
These results indicate that p38 MAP kinase plays an important role in the TNF-alpha-activated signaling pathway which regulates RANTES production by human pulmonary vascular endothelial cells.
Hashimoto
S
S
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Gon
Y
Y
Asai
Y
Y
Asai
Y
Y
Machino
T
T
Jibiki
I
I
Takeshita
I
I
Anazawa
H
H
Horie
T
T
D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011651:Pulmonary Artery / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D018946:Chemokine CCL5; D007093:Imidazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580