Anti-inflammatory effects of synthetic compound KT-14480 in lipopolysaccharide-stimulated microglia cells

Abstract

Objectives Neurodegenerative diseases have a prominent inflammatory component. Several synthetic fluorovinyloxyacetamide derivatives were screened by microglia cell-based assay in order to identify novel compounds that inhibit the inflammatory activation of microglia. Methods Microglia cell-based nitric oxide assay was employed to screen the compounds. RT-PCR and ELISA were conducted to evaluate the expression of inflammatory gene expression. Molecular mechanisms were determined by western blot analysis, immunocytochemistry, EMSA, and microglia/neuroblastoma cocultures. Key findings A fluorovinyloxyacetamide compound KT-14480 significantly suppressed nitric oxide production in lipopolysaccharide-stimulated microglia cells. KT-14480 also suppressed the secretion and expression of several inflammatory mediators such as tumour necrosis factor-α, interleukin-1β and inducible nitric oxide synthase. Additional studies showed that these inhibitory effects were accompanied by the suppression of nuclear factor-κB and neuroprotection in the microglia/neuroblastoma coculture. Conclusions Our results indicate that the anti-inflammatory compound KT-14480 may be a novel therapeutic drug candidate against neuroinflammatory diseases. © 2010 Royal Pharmaceutical Society of Great Britain.