Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation
S. Hashimoto et al., Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation, AM J R CRIT, 161(1), 2000, pp. 280-285
Air pollutants including diesel exhaust particles (DEPs) have been shown to
enhance allergic responses. DEPs stimulate airway epithelial cells to prod
uce various cytokines; however, the intracellular signal transduction pathw
ay and the involvement of reduction and oxidation (redox) control in DEP-ac
tivated signaling have not been determined. In the present study, we theref
ore examined the role of p38 mitogen-activated protein (MAP) kinase in DEP-
induced interleukin 8 (IL-8) and RANTES production by human bronchial epith
elial cells (BECs) in order to clarify the intracellular signal transductio
n pathway that regulates IL-8 and RANTES production. In addition, we also e
xamined the effect of a thiol-reducing agent, N-acetylcysteine (NAC), on DE
P-induced p38 MAP kinase activation and cytokine production in order to cla
rify the redox control mechanism in DEP-induced p38 MAP kinase activation a
nd IL-8 and RANTES production. The results showed that DEP induced IL-8 and
RANTES production and the threonine and tyrosine phosphorylation of p38 MA
P kinase, reflecting the activation of p38 MAP kinase in BECs. SB 203580, a
s the specific inhibitor of p38 MAP kinase activity, inhibited DEP-induced
IL-8 and RANTES production. NAC inhibited DEP-induced p38 MAP kinase activa
tion and IL-8 and RANTES production. These results indicate that p38 MAP ki
nase plays an important role in the DEP-activated signaling pathway that re
gulates IL-8 and RANTES production by BECs and that the cellular redox stat
e is critical for DEP-induced p38 MAP kinase activation reading to IL-8 and
RANTES production.