T Lymphocytes as Targets of Statins: Molecular Mechanisms and Therapeutic Perspectives

Authors: Ghittoni, Raffaella; Enea Lazzerini, Pietro; Laghi Pasini, Franco; Baldari, Cosima T.

Source: Inflammation & Allergy - Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy), Volume 6, Number 1, March 2007 , pp. 3-16(14)

Publisher: Bentham Science Publishers

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Abstract:

Statins are cholesterol-lowering drugs extensively used for primary and secondary prevention of cardiovascular events related to hypercholesterolemia. Because of their capacity to inhibit HMG-CoA reductase, statins also block the production of isoprenoids required for post-translational modification of proteins such as Ras superfamily GTPases, which are master regulators in signaling pathways triggered by surface receptors. As such, statins have pleiotropic effects on many cell types. In the immune system, statins harbor strong anti-inflammatory properties, which result from their capacity to interfere with the activation of proinflammatory cells, including macrophages and endothelial cells. More recently, T-lymphocytes have been identified as cellular targets of statins. Here we shall review recent findings, which document an inhibitory activity of statins on T-cell activation, proliferation, differentiation to Th1 cells and migration across the bloodbrain barrier. The therapeutic perspectives of these findings, based on animal models and ongoing clinical trials, will also be discussed.

Keywords: HMG-CoA reductase; prenylation; GTPase; Th1/Th2; autoimmune disease; allograft rejection; animal model; clinical trial

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152807780077291

Affiliations: 1: Department of Evolutionary Biology, Via Aldo Moro 2, 53100 Siena, Italy.

Publication date: 2007-03-01

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Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

T Lymphocytes as Targets of Statins: Molecular Mechanisms and Therapeutic Perspectives

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