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

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-kappa B (NF-kappa B), interferon beta (IFN beta) 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-beta (TRIF)-dependent signaling pathway of TLRs. (C) 2013 Published by Elsevier Inc.