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-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.

• Authors: Jiyeon Ock, Kyoungho Suk
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 62 Issue 2 Pg. 279-85 (Feb 2010) ISSN: 2042-7158 [Electronic] England
• PMID: 20487209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetanilides
• Anti-Inflammatory Agents, Non-Steroidal
• KT 14480
• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• lipopolysaccharide, Escherichia coli O111 B4
• Nitric Oxide
• Mitogen-Activated Protein Kinases

Topics

• Acetanilides (pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blotting, Western
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Coculture Techniques
• Electrophoretic Mobility Shift Assay
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• Gene Expression (drug effects)
• Lipopolysaccharides (toxicity)
• Mice
• Microglia (drug effects, immunology, pathology)
• Mitogen-Activated Protein Kinases (metabolism)
• Molecular Structure
• NF-kappa B (antagonists & inhibitors, biosynthesis)
• Nitric Oxide (biosynthesis)
• Rats
• Tumor Necrosis Factor-alpha (genetics)