Lovastatin modulation of microglial activation via suppression of functional CD40 expression

Journal of Neuroscience Research
Kirk P TownsendJ Tan

Abstract

Recent studies have shown that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) possess antiinflammatory and immunomodulatory properties, distinct from their action of lowering serum lipid levels. Moreover, results of epidemiological studies suggest that long-term use of statins is associated with a decreased risk for Alzheimer's disease (AD). Interestingly, lovastatin (one of the most commonly used anticholesterol drugs) treatment of vascular-derived cells has been reported to antagonize activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, and it is well known that the JAK/STAT pathway plays a central role in interferon-gamma (IFN-gamma)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-gamma and amyloid-beta (Abeta) peptide. Moreover, it has been shown that CD40 signaling is critically involved in microglia-related immune responses in the CNS. In this study, we examined the putative role of lovastatin in modulation of CD40 expression and its signaling in cultured microglia. RT-PCR, Western immunoblotting, and flow cytometry data show that lovastatin suppres...Continue Reading

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