-Statins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-b1 (TGF-b1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-b1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-b responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1–20 lM). Pravastatin (1–20 lM) induced a dose-dependent increase in TGF-b1 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 lM. This last effect was reversed by a mouse monoclonal anti-TGF-b1 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 lM) which was inhibited by a mouse monoclonal anti-TGF-b1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-b1 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.
PRAVASTATIN UP-REGULATES TGF-B1 IN THP-1 HUMAN MACROPHAGES :EFFECT ON SCAVENGER RECEPTOR CLASS A EXPRESSION
MINCIONE, Gabriella;DI MARCANTONIO, Maria Carmela;CUCCURULLO, Franco;PORRECA, Ettore
2004-01-01
Abstract
-Statins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-b1 (TGF-b1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-b1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-b responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1–20 lM). Pravastatin (1–20 lM) induced a dose-dependent increase in TGF-b1 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 lM. This last effect was reversed by a mouse monoclonal anti-TGF-b1 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 lM) which was inhibited by a mouse monoclonal anti-TGF-b1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-b1 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
