alitretinoin and 7-ketocholesterol

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.

Topics: Alitretinoin; Animals; Cells, Cultured; Cholesterol; Farnesol; Hydroxycholesterols; Hydroxysteroids; Ketocholesterols; Lipopolysaccharides; Liver X Receptors; Macrophages; Male; Mevalonic Acid; Mice; Mice, Inbred C57BL; Orphan Nuclear Receptors; Receptors, Cytoplasmic and Nuclear; Retinoid X Receptors; Transforming Growth Factor beta; Tretinoin