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Am J Physiol Heart Circ Physiol 281: H661-H668, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 2, H661-H668, August 2001

Endotoxin stimulated cytokine production in rat vascular smooth muscle cells

Kristina Detmer1, Zhongbiao Wang1, Debra Warejcka2, Sandra K. Leeper-Woodford1, and Walter H. Newman1,2

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-alpha (TNF-alpha ) mRNA increased in response to LPS. Activation of nuclear factor-kappa B (NF-kappa B) presumably results in NF-kappa B binding to regulatory regions of target genes and activating transcription. We therefore compared the kinetics of NF-kappa B activation, cytokine message production, and TNF-alpha secretion. Maximum active NF-kappa 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-alpha mRNA at 60 min, and increased IL-1 mRNA at 120 min. Secretion of TNF-alpha was dependent on LPS concentration and was first detected 120 min after LPS addition. Aspirin, which has been shown to inhibit NF-kappa B activation and cytokine secretion in other cell types, did not inhibit NF-kappa B activation or TNF-alpha secretion. However, aspirin reduced the amount of both TNF-alpha and IL-6 mRNA present 30 min after LPS addition by half (P < 0.05).

atherosclerosis; nuclear factor-kappa B; tumor necrosis factor-alpha ; aspirin; cytokine gene transcription


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