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1 Division of Basic Medical Sciences and 2 Department of Surgery, Mercer University School of Medicine, Macon, Georgia 31207
Because inflammatory processes may promote the
development of atherosclerosis, we examined the activation of cytokine
genes in rat vascular smooth muscle cells in vitro after treatment with bacterial lipopolysaccharide (LPS). Interleukin-1 (IL-1), IL-6 and
tumor necrosis factor-
(TNF-
) mRNA increased in response to LPS.
Activation of nuclear factor-
B (NF-
B) presumably results in
NF-
B binding to regulatory regions of target genes and activating transcription. We therefore compared the kinetics of NF-
B
activation, cytokine message production, and TNF-
secretion. Maximum
active NF-
B was found at 30 min after the addition of LPS and
decreased thereafter. Increased IL-6 mRNA was detected at 30 min,
increased TNF-
mRNA at 60 min, and increased IL-1 mRNA at 120 min.
Secretion of TNF-
was dependent on LPS concentration and was first
detected 120 min after LPS addition. Aspirin, which has been shown to
inhibit NF-
B activation and cytokine secretion in other cell types,
did not inhibit NF-
B activation or TNF-
secretion. However,
aspirin reduced the amount of both TNF-
and IL-6 mRNA present 30 min after LPS addition by half (P < 0.05).
atherosclerosis; nuclear factor-
B; tumor necrosis factor-
; aspirin; cytokine gene transcription
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