Intracellular glutathione regulates tumour necrosis factor-alpha-induced p38 MAP kinase activation and RANTES production by human bronchial epithelial cells
S. Hashimoto et al., Intracellular glutathione regulates tumour necrosis factor-alpha-induced p38 MAP kinase activation and RANTES production by human bronchial epithelial cells, CLIN EXP AL, 31(1), 2001, pp. 144-151
Background RANTES plays an important role in the production of allergic inf
lammation of the airway through its chemotactic activity for eosinophils. T
he cellular reduction and oxidation (redox) changes are involved in the act
ivation of p38 mitogen-activated protein (MAP) kinase and the induction of
cytokine expression. It has previously been shown that tumour necrosis fact
or (TNF)-MA activates p38 mitogen-activated protein (MAP) kinase to produce
cytokine, including RANTES, that N-acetylcysteine (NAC) attenuates cytokin
e production by human bronchial epithelial cells (BECs), and that sensitivi
ty to TNF alpha is inversely correlated with cellular redox state. However,
a role of cellular redox regulated by intracellular glutathione (GSH) in T
NF alpha -induced p38 MAP kinase activation and p38 MAP kinase-mediated RAN
TES production by human BECs has not been determined.
Objective Human BECs were exposed to NAG or buthionine sulfoximine (BSO). T
NF alpha- induced p38 MAP kinase activation and p38 MAP kinase-mediated RAN
TES production by human BECs were then examined in order to clarify these i
ssues.
Results The results showed that: NAC attenuated TNF alpha -induced p38 MAP
kinase activation and RANTES production; SE 203580 as the specific inhibito
r of p38 MAP kinase activity attenuated TNF-alpha -induced RANTES productio
n; BSO facilitated TNF-alpha -induced p38 MAP kinase activation and RANTES
production; SE 203580 attenuated BSO-mediated facilitation of TNF-alpha -in
duced RANTES production; and the intracellular GSH increased in NAG-treated
cells, whereas the intracellular GSH was reduced in BSO-treated cells.
Conclusions These results indicate that cellular redox regulated by GSH is
critical for TNF-alpha -induced p38 MAP kinase activation and p38 MAP kinas
e-mediated RANTES production by human BECs.