MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a novel synthetic compound derived from epothilone, suppresses nuclear factor-kappaB-mediated cytokine expression in lipopolysaccharide-stimulated BV-2 microglia

J Pharmacol Sci. 2010;112(2):158-66. doi: 10.1254/jphs.09239fp. Epub 2010 Feb 4.

Abstract

The effects of MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a novel synthetic compound derived from epothilone, was investigated for its effects on the expression of proinflammatory mediators in lipopolysaccharide-stimulated BV-2 microglia. MMHD attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA and protein without affecting cell viability. Moreover, MMHD suppressed nuclear factor-kappaB (NF-kappaB) activation via the translocation of p65 into the nucleus. These results indicate that MMHD exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes through the NF-kappaB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / genetics
  • Cytokines / drug effects*
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / genetics
  • Protein Transport / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Thiazoles / pharmacology*
  • Transcription Factor RelA / metabolism

Substances

  • 2-methyl-1-(2-methylthiazol-4-yl)hexa-1,5-dienol
  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Thiazoles
  • Transcription Factor RelA
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2