Inflammation may be one of the independent risk factors contributing to many neurological diseases. Moreover, there is an emerging body of data indicating that
statins may have neuroprotective action. Recent studies suggest that CD40-CD40
ligand (
CD40L) system is proven to be an important mediator of several auto-immune and chronic
inflammation diseases. To address whether
lovastatin produces neuroprotection as a potential novel anti-inflammatory pathway through the inhibition of CD40 expression, we examined the possible effects of
lovastatin on expression of CD40, apoptosis, level of
nitric oxide (NO) and
nitric oxide synthase (NOS) activity induced by
tumor necrosis factor alpha (
TNF-alpha) in the cerebral vascular endothelial cells (CVECs) involved in
cerebrovascular diseases. Preincubation with
lovastatin (10(-7), 10(-6) and 10(-5) mol/l) for 24 hours (h) protected CVECs from
TNF-alpha-induced decrease of cellular viability. Further,
lovastatin inhibited the
TNF-alpha-induced increases of NO level, NOS activity, apoptotic cells and CD40 expression in a dose-dependent manner, and anti-CD40 antibody also inhibited the cellular apoptosis induced by
TNF-alpha. In conclusion, our data provide evidence to support a direct pro-inflammatory effect of CD40-CD40L signaling pathway in CVECs, and
lovastatin possesses an anti-inflammatory effect independent of its
lipid-lowering action involved in the
cerebrovascular diseases.