Anti-inflammatory benzene diamine compound inhibited toll-like receptor 4-mediated inducible nitric oxide synthase expression and nuclear factor-kappa B activation

Biol Pharm Bull. 2005 May;28(5):908-11. doi: 10.1248/bpb.28.908.

Abstract

Toll-like receptor 4 (TLR4) is known to play an important role in innate immune responses. In the present study, chemically synthetic compound of N(1)-benzyl-4-methylbenzene-1,2-diamine (BMD) was discovered to inhibit nitric oxide (NO) production in macrophages RAW 264.7 stimulated with lipopolysaccharide (LPS) or fibronectin as TLR4 activators. The BMD compound attenuated LPS-induced synthesis of both mRNA and protein of NO synthase (iNOS), and inhibited LPS or fibronectin-mediated iNOS promoter activity, indicating that the compound down-regulated iNOS expression at transcription level. As a mode of the anti-inflammatory action shown by BMD compound, inhibitory effect on nuclear factor (NF)-kappaB activation was also investigated in macrophages RAW 264.7 stimulated with the TLR4 activators.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Benzene / chemistry
  • Benzene / pharmacology*
  • Cell Line
  • Diamines / chemistry
  • Diamines / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Mice
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / biosynthesis*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diamines
  • Enzyme Inhibitors
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Benzene