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


RESULTS
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.
Ock
Jiyeon
J
Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu, Korea.
Suk
Kyoungho
K
D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000083:Acetanilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; C553099:KT 14480; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases