Suppression of the TRIF-dependent signaling pathway of Toll-like receptor by CDr10b in RAW264.7 macrophages

Int Immunopharmacol. 2015 Sep;28(1):29-33. doi: 10.1016/j.intimp.2015.05.017. Epub 2015 May 21.

Abstract

Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and play a critical role in innate immune responses. TLR signaling pathways can be largely classified as either myeloid differential factor 88 (MyD88)- or toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. Compound of Designation red 10 binding (CDr10b) was synthesized to investigate its role in neuroinflammatory diseases. This study was conducted to determine whether CDr10b can affect TLR signaling pathways. CDr10b suppressed NF-κB activation as well as COX-2 and iNOS expression induced by TLR3 or TLR4 agonists. CDr10b also suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. These results indicate that CDr10b can modulate the TRIF-dependent pathway of TLRs and has the potential to become a new therapeutic drug for chronic inflammatory diseases.

Keywords: CDr10b; IP-10; IRF3; TRIF; Toll-like receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / drug effects*
  • Animals
  • Boron Compounds / chemical synthesis
  • Boron Compounds / pharmacology*
  • Chemokine CXCL10 / biosynthesis
  • Cyclooxygenase 2 / drug effects
  • Interferon Regulatory Factor-3 / biosynthesis
  • Interferon Regulatory Factor-3 / genetics
  • Macrophages / drug effects
  • Mice
  • NF-kappa B / drug effects
  • Nitric Oxide Synthase Type II / drug effects
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Toll-Like Receptor 3 / agonists
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptors / antagonists & inhibitors*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Boron Compounds
  • CDr10b compound
  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Interferon Regulatory Factor-3
  • NF-kappa B
  • TICAM-1 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Tbk1 protein, mouse
  • Protein Serine-Threonine Kinases