Statins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-β1 (TGF-β1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-β1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-β responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1-20μM). Pravastatin (1-20μM) induced a dose-dependent increase in TGF-β1 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 10μM. This last effect was reversed by a mouse monoclonal anti-TGF-β1 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 (1-20μM) which was inhibited by a mouse monoclonal anti-TGF-β1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-β1 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. © 2003 Elsevier Inc. All rights reserved.
Soluble thrombomodulin and vascular adhesion molecule-1 are associated to leptin plasma levels in obese patients.
PORRECA, Ettore;MORETTA, VALERIA;DI NISIO, Marcello;CUCCURULLO, Franco
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-β1 (TGF-β1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-β1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-β responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1-20μM). Pravastatin (1-20μM) induced a dose-dependent increase in TGF-β1 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 10μM. This last effect was reversed by a mouse monoclonal anti-TGF-β1 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 (1-20μM) which was inhibited by a mouse monoclonal anti-TGF-β1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-β1 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. © 2003 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
