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1


Departments of
*
Physiology and
Clinical Hematology, Osaka City University Medical School, Osaka, Japan
We investigated activation of mitogen-activated protein kinase
(MAPK) subtype cascades in human neutrophils stimulated by IL-1
.
IL-1
induced phosphorylation and activation of p38 MAPK and
phosphorylation of MAPK kinase-3/6 (MKK3/6). Maximal activation of p38
MAPK was obtained by stimulation of cells with 300 U/ml IL-1
for 10
min. Extracellular signal-regulated kinase (ERK) was faintly
phosphorylated and c-Jun N-terminal kinase (JNK) was not phosphorylated
by IL-1
. IL-1
primed neutrophils for enhanced release of
superoxide (O2-) stimulated by FMLP in
parallel with increased phosphorylation of p38 MAPK. IL-1
also
induced O2- release and up-regulation of CD11b
and CD15, and both responses were inhibited by SB203580 (p38 MAPK
inhibitor), suggesting that p38 MAPK activation mediates
IL-1
-induced O2- release and up-regulation
of CD11b and CD15. Combined stimulation of neutrophils with IL-1
and
G-CSF, a selective activator of the ERK cascade, resulted in the
additive effects when the priming effect and phosphorylation of p38
MAPK and ERK were assessed. IL-1
induced phosphorylation of ERK and
JNK as well as p38 MAPK in human endothelial cells. These findings
suggest that 1) in human neutrophils the MKK3/6-p38 MAPK cascade is
selectively activated by IL-1
and activation of this cascade
mediates IL-1
-induced O2- release and
up-regulation of CD11b and CD15, and 2) the IL-1R-p38 MAPK pathway and
the G-CSF receptor-ERK pathway work independently for activation of
neutrophils.
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