Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

Autor: Glazenburg Lisa, Chesik Daniel, Wilczak Nadine, Zeinstra Esther, Kroese Frans GM, De Keyser Jacques
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 3, Iss 1, p 16 (2006)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/1742-2094-3-16
Popis: Abstract Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors) are being studied as possible candidates for multiple sclerosis (MS) therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN)-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS.
Databáze: Directory of Open Access Journals