Regulation by intracellular glutathione of TNF-alpha-induced p38 MAP kinase activation and RANTES production by human pulmonary vascular endothelial cells
S. Hashimoto et al., Regulation by intracellular glutathione of TNF-alpha-induced p38 MAP kinase activation and RANTES production by human pulmonary vascular endothelial cells, ALLERGY, 55(5), 2000, pp. 463-469
Background: We have previously shown that p38 mitogen-activated protein (MA
P) kinase regulates tumor necrosis factor-alpha (TNF-alpha)-induced RANTES
production by human pulmonary vascular endothelial cells, and that sensitiv
ity to TNF-alpha is inversely correlated with cellular reduction and oxidat
ion (redox) state. However, a regulatory role of intracellular glutathione
(GSH) in TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-med
iated RANTES production has not been determined. In the present study, ther
efore, we extended our previous studies and focused on redox regulation on
p38 MAP kinase activation.
Methods: Human pulmonary vascular endothelial cells were exposed to N-acety
lcysteine (NAC) or buthionine sulfoximine (BSO), and then TNF-alpha-induced
p38 MAP kinase activation and p38 MAP kinase-mediated RANTES production we
re determined.
Results: The results showed that
1) NAC attenuated TNF-alpha-induced p38MAP kinase activation and RANTES pro
duction
2) SE 203580 as the specific inhibitor of p38 MAP kinase activity attenuate
d TNF-alpha-induced RANTES production
3) BSO facilitated TNF-alpha-induced p38 MAP kinase activation and RANTES p
roduction
4) SE 203580 attenuated BSO-mediated facilitation of TNF-alpha-induced RANT
ES production.
Conclusions: These results indicated that TNF-alpha-induced p38 MAP kinase
activation and p38 MAP kinase-mediated RANTES production by human pulmonary
vascular endothelial cells are inversely regulated by intracellular GSH le
vels.