Modulation of human T cells signaling transduction by lovastatin.
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.
Cheng
Shu-Meng
SM
Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center No 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC. chengsm@cm1.hinet.net
Lai
Jenn-Haung
JH
Yang
Shih-Ping
SP
Tsao
Tien-Ping
TP
Ho
Ling-Jun
LJ
Liou
Jun-Ting
JT
Cheng
Cheng-Chung
CC
D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D016328:NF-kappa B / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011758:Pyrroles; D018808:Transcription Factor AP-1; D008148:Lovastatin; D000069059:Atorvastatin