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Journal of Lipid Research, Vol 35, 271-278, Copyright © 1994 by Lipid Research, Inc.
G Renier, E Skamene, JB DeSanctis and D Radzioch
In view of the suppressive effect of tumor necrosis factor alpha (TNF
alpha) on lipoprotein lipase (LPL) and of the potential proatherogenic
effects of these two macrophage secretory products, we have tested the
possibility that LPL could modulate the production of TNF alpha. Treatment
of macrophages with lipoprotein lipase induced tumor necrosis factor alpha
gene expression and protein secretion. Maximal increase of TNF alpha mRNA
levels occurred after a 3-h treatment with 200 ng/ml LPL. An additive
effect of interferon gamma (IFN gamma) was observed on LPL-induced TNF
alpha mRNA expression. De novo mRNA synthesis was required for induction of
TNF alpha mRNA by LPL as no induction was observed when macrophages were
pretreated with actinomycin D before adding LPL. We further established
that LPL induced the transcription of the TNF alpha gene in macrophages. We
also found that LPL caused the nuclear migration of one member of the NFkB
family that appears to bind to a site in the murine TNF alpha gene
promoter. Furthermore, we demonstrated that the treatment of macrophages
with LPL increased the stability of TNF alpha mRNA. These results show that
the TNF alpha gene induction in response to LPL involves both
transcriptional activation and the enhancement of TNF alpha mRNA stability.
Overall, our data demonstrate a new role for LPL, that of modulating
macrophage TNF alpha gene expression. This effect may represent one of the
mechanisms by which LPL may favor the development of atherosclerosis.
ARTICLES
Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase
Department of Experimental Medicine, McGill Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
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