Simvastatin Nanoparticles Reduce Inflammation in LPS-Stimulated Alveolar Macrophages

1.0 Abstract Simvastatin (SV) is widely used as lipid- lowering medication that has also been found to have beneficial immuno-modulatory effects for treatment of chronic lung diseases. Although its anti-inflammatory activity has been investigated, its underlying mechanisms have not yet been clearly elucidated. In this study, the anti-inflammatory and anti-oxidant effects and mechanism of simvastatin nanoparticles (SV-NPs) on lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) NR8383 cells were investigated. Quantitative cellular uptake of SV-NPs, the production of inflammatory mediators (interleukin (IL)-6, tumour necrosis factor (TNF) and monocyte chemoattractant protein-1 (MCP-1)), and oxidative stress (nitric oxide, NO) were tested. Furthermore, the involvement of the Nuclear factor KB (NF-KB) signaling pathway in activation of inflammation in AM and the efficacy of SV were visualized using immunofluorescence. Results indicated that SV-NPs exhibit a potent inhibitory effect on NO production and secretion of inflammatory cytokine in inflamed AM, without affecting cell viability. The enhanced anti-inflammatory activity of SV-NPs is likely due to SV improved chemical- physical stability and higher cellular uptake into AM. The study also indicates that SV targets the inflammatory and oxidative response of AM, through inactivation of the NF-ΚB signalling pathway, supporting the pharmacological basis of SV for treatment of chronic inflammatory lung diseases.