1. Effects of cholesterol and nuclear hormone receptor agonists on the production of transforming growth factor-beta in macrophages.
- Author
-
Schwartz YSh, Khoshchenko OM, Dushkin MI, and Feofanova NA
- Subjects
- Alitretinoin, Animals, Cells, Cultured, Cholesterol pharmacology, Farnesol pharmacology, Hydroxycholesterols pharmacology, Hydroxysteroids pharmacology, Ketocholesterols pharmacology, Lipopolysaccharides pharmacology, Liver X Receptors, Male, Mevalonic Acid analogs & derivatives, Mevalonic Acid pharmacology, Mice, Mice, Inbred C57BL, Orphan Nuclear Receptors agonists, Retinoid X Receptors agonists, Tretinoin pharmacology, Macrophages drug effects, Macrophages metabolism, Receptors, Cytoplasmic and Nuclear agonists, Transforming Growth Factor beta metabolism
- 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.
- Published
- 2009
- Full Text
- View/download PDF