title: Effects of cholesterol and nuclear hormone receptor agonists on the production of transforming growth factor-beta in macrophages.
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.
authors.affiliation: Institute of Therapy, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk, Russia. YShSchwartz@mail.ru
authors.forename: Ya Sh
authors.initials: YSh
authors.lastname: Schwartz
authors.forename: O M
authors.initials: OM
authors.lastname: Khoshchenko
authors.forename: M I
authors.initials: MI
authors.lastname: Dushkin
authors.forename: N A
authors.initials: NA
authors.lastname: Feofanova
mesh_terms: 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
chemical_list: 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