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Molecular and Cellular Biology, March 1999, p. 1950-1960, Vol. 19, No. 3
Laboratory of Medical Chemistry/Medical
Oncology,1 Laboratory of Fundamental
Virology,2 and Laboratory of
Pathology,3 University of Liège,
Liège, Belgium
Received 16 July 1998/Returned for modification 26 August
1998/Accepted 30 November 1998
We previously reported that the role of reactive oxygen
intermediates (ROIs) in NF-
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Reactive Oxygen Intermediate-Dependent NF-
B
Activation by Interleukin-1
Requires 5-Lipoxygenase or NADPH
Oxidase Activity
B activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types
are yet to be determined and might include 5-lipoxygenase (5-LOX) and
NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are
coexpressed in lymphoid cells but not in monocytic or epithelial cells.
Stimulation of lymphoid cells with interleukin-1
(IL-1
) led to
ROI production and NF-
B activation, which could both be blocked by
antioxidants or FLAP inhibitors, confirming that 5-LOX was the source
of ROIs and was required for NF-
B activation in these cells. IL-1
stimulation of epithelial cells did not generate any ROIs and NF-
B
induction was not influenced by 5-LOX inhibitors. However,
reintroduction of a functional 5-LOX system in these cells allowed ROI
production and 5-LOX-dependent NF-
B activation. In monocytic cells,
IL-1
treatment led to a production of ROIs which is independent of
the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway
involves the Rac1 and Cdc42 GTPases, two enzymes which are not required
for NF-
B activation by IL-1
in epithelial cells. In conclusion,
three different cell-specific pathways lead to NF-
B activation by
IL-1
: a pathway dependent on ROI production by 5-LOX in lymphoid
cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a
pathway requiring ROI production by NADPH oxidase in monocytic cells.
*
Corresponding author. Mailing address: Medical
Oncology, CHU B35, Sart-Tilman, Université de Liège, 4000 Liège, Belgium. Phone: 32-4-3662482. Fax: 32-4-3664534. E-mail:
vbours{at}ulg.ac.be.
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