Phenethyl isothiocyanate regulates inflammation through suppression of the TRIF-dependent signaling pathway of Toll-like receptors

Life Sci. 2013 Apr 19;92(13):793-8. doi: 10.1016/j.lfs.2013.02.012. Epub 2013 Feb 27.

Abstract

Aims: The aim of this study was to evaluate the therapeutic potential of the phenethyl isothiocyanate (PEITC) in Toll-like receptor (TLR) signaling pathways.

Main methods: To evaluate the cytotoxic nature of PEITC in RAW 264.7 cells, cytotoxicity was determined using the MTS cell viability assay. RAW264.7 cells were transfected with a nuclear factor-κB (NF-κB), interferon β (IFNβ) PRDIII-I, or interferon inducible protein-10 (IP-10) luciferase plasmid and then luciferase enzyme activities were determined by luciferase assay. The expression of inducible nitric oxide synthase (iNOS) and phosphorylation of interferon regulatory factor 3 (IRF3) were determined by Western blotting. The levels of IP-10 were determined with culture medium by using an IP-10 enzyme-linked immunosorbent assay (ELISA) kit.

Key findings: PEITC suppressed the activation of IRF3 and the expression of IP-10 induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]).

Significance: TLRs play an important role in the induction of innate immune responses for host defense against invading microbial pathogens. PEITC found in cruciferous vegetables has an effect on treatment of many chronic diseases. Our results suggest that beneficial effects of PEITC on chronic inflammatory diseases are mediated through modulation of Toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent signaling pathway of TLRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / immunology*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Cell Line
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Interferon Regulatory Factor-3 / immunology
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Lipopolysaccharides / immunology
  • Mice
  • Monocytes / drug effects
  • Monocytes / immunology
  • NF-kappa B / immunology
  • Poly I-C / immunology
  • Signal Transduction / drug effects
  • Toll-Like Receptors / immunology*
  • Vegetables / chemistry

Substances

  • Adaptor Proteins, Vesicular Transport
  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Interferon Regulatory Factor-3
  • Isothiocyanates
  • Lipopolysaccharides
  • NF-kappa B
  • TICAM-1 protein, mouse
  • Toll-Like Receptors
  • phenethyl isothiocyanate
  • Poly I-C