Modulation of human T cells signaling transduction by lovastatin

Int J Cardiol. 2010 Apr 1;140(1):24-33. doi: 10.1016/j.ijcard.2008.10.044. Epub 2008 Nov 28.

Abstract

Statins are applied clinically to treat hypercholesterolemia and proposed to have some kinds of anti-inflammatory properties for reducing the incidence of atherosclerosis-related cardiovascular events. However, it was rarely known about statins on the signal transduction on human primary T cells. To gain insight into the mechanism of statins on human T cells, we investigated the effects of both lovastatin and atorvastatin on activated human primary T cells. The human primary T cells from the blood of normal human beings were isolated. We found that lovastatin, but not atorvastatin, can dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, and interferon-gamma from activated human T cells. Neither lovastatin nor atorvastatin can regulate the TNF-alpha production on both activated human T cells and monocytes. Molecular investigation was performed that lovastatin, but not atorvastatin, could down-regulate both activator protein-1 and NF-kappaB DNA binding activities, assessed by electrophoretic mobility shift assay. Our observations may extend potential and differential therapeutic mechanisms of lovastatin with cell-mediated capacity to prevent or treat some of inflammation related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin
  • Dose-Response Relationship, Drug
  • Down-Regulation / physiology
  • Electrophoretic Mobility Shift Assay
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lovastatin / pharmacology*
  • NF-kappa B / physiology
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*
  • Transcription Factor AP-1 / physiology

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NF-kappa B
  • Pyrroles
  • Transcription Factor AP-1
  • Lovastatin
  • Atorvastatin