Effects of cholesterol and nuclear hormone receptor agonists on the production of transforming growth factor-beta in macrophages
Bull Exp Biol Med. 2009 Sep;148(3):406-9.
doi: 10.1007/s10517-010-0724-7.
[Article in
English,
Russian]
Affiliation
- 1 Institute of Therapy, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk, Russia. YShSchwartz@mail.ru
Abstract
We studied the effects of cholesterol, its oxidized derivatives mevalonate, and nuclear receptor agonists LXR, RXR, and FXR on the production of transforming growth factor-beta1 (TGF- beta1) by macrophages. After recruiting of macrophage monocytes into the focus of inflammation, the production of TGF-beta1 increased by 3.5 times in comparison with control macrophages. Cholesterol diet stimulated the production of TGF-beta1 by 2.5 times. Cholesterol directly stimulated macrophage production of TGF-beta1 in vitro, while addition of mevalonate to the incubation medium effectively reduced this induced production. Agonists of nuclear receptor sharply reduced the production of TGF-beta1 in recruited macrophages. Under conditions of inflammation, hypercholesterolemia can be a factor of fibrogenesis due to TGF-beta1 induction in macrophages, which depends on the products of mevalonate biochemical chain.
MeSH terms
-
Alitretinoin
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Animals
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Cells, Cultured
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Cholesterol / pharmacology
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Farnesol / pharmacology
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Hydroxycholesterols / pharmacology
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Hydroxysteroids / pharmacology
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Ketocholesterols / pharmacology
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Lipopolysaccharides / pharmacology
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Liver X Receptors
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Macrophages / drug effects*
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Macrophages / metabolism*
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Male
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Mevalonic Acid / analogs & derivatives
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Mevalonic Acid / pharmacology
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Mice
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Mice, Inbred C57BL
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Orphan Nuclear Receptors / agonists
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Receptors, Cytoplasmic and Nuclear / agonists*
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Retinoid X Receptors / agonists
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Transforming Growth Factor beta / metabolism*
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Tretinoin / pharmacology
Substances
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Hydroxycholesterols
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Hydroxysteroids
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Ketocholesterols
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Lipopolysaccharides
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Liver X Receptors
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Retinoid X Receptors
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Transforming Growth Factor beta
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lipopolysaccharide, Escherichia coli O111 B4
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Alitretinoin
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Farnesol
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Tretinoin
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mevalonolactone
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25-hydroxycholesterol
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Cholesterol
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7-ketocholesterol
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Mevalonic Acid