Pravastatin up-regulates transforming growth factor-beta1 in THP-1 human macrophages: effect on scavenger receptor class A expression.
Statins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-beta1 (TGF-beta1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-beta1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-beta responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1-20 microM). Pravastatin (1-20 microM) induced a dose-dependent increase in TGF-beta1 mRNA expression and protein production in THP-1 cells. PMA-induced SRA gene and protein expression was suppressed by pravastatin with a mean 3-fold decrease at 10 microM. This last effect was reversed by a mouse monoclonal anti-TGF-beta1 neutralizing antibody. PD98059, a specific inhibitor of MAP kinase cascade, completely reversed pravastatin-induced SRA down-regulation. p44 and p42 isoforms showed a dose-dependent phosphorylation after treatment with pravastatin (1-20 microM) which was inhibited by a mouse monoclonal anti-TGF-beta1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-beta1 expression which may be in involved in down-regulation of SRA expression in THP-1 cell cultures. A new pathway for pravastatin effects in atherogenesis can be suggested.
Baccante
Giovanna
G
Department of Medicine and Sciences of Aging, "G. D'Annunzio" University, Chieti, Italy.
Mincione
Gabriella
G
Di Marcantonio
Maria Carmela
MC
Piccirelli
Alessandro
A
Cuccurullo
Franco
F
Porreca
Ettore
E
D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D017035:Pravastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases; D017035:Pravastatin