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Published on: July 17, 2016
Anti-inflammatory effects of synthetic compound KT-14480 in lipopolysaccharide-stimulated microglia cells
1Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu, Korea.
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-alpha, interleukin-1beta and inducible nitric oxide synthase. Additional studies showed that these inhibitory effects were accompanied by the suppression of nuclear factor-kappaB 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.
