Effects of cholesterol and nuclear hormone receptor agonists on the production of transforming growth factor-beta in macrophages.
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.
Schwartz
Ya Sh
YSh
Institute of Therapy, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk, Russia. YShSchwartz@mail.ru
Khoshchenko
O M
OM
Dushkin
M I
MI
Feofanova
N A
NA
D000077556:Alitretinoin; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D006914:Hydroxysteroids / Q000494:pharmacology; D007653:Ketocholesterols / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000819:agonists; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D047488:Retinoid X Receptors / Q000819:agonists; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D006888:Hydroxycholesterols; D006914:Hydroxysteroids; D007653:Ketocholesterols; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D016212:Transforming Growth Factor beta; C440499:lipopolysaccharide, Escherichia coli O111 B4; D000077556:Alitretinoin; D005204:Farnesol; D014212:Tretinoin; C015367:mevalonolactone; C007997:25-hydroxycholesterol; D002784:Cholesterol; C003001:7-ketocholesterol; D008798:Mevalonic Acid