Open AccessAnti‐inflammatory potential of allyl‐isothiocyanate – role of Nrf2, NF‐ κ B and microRNA‐155
Author(s) -
Wagner Anika Eva,
BoeschSaadatmandi Christine,
Dose Janina,
Schultheiss Gerhard,
Rimbach Gerald
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01367.x
Subject(s) - allyl isothiocyanate , lipopolysaccharide , isothiocyanate , inflammation , heme oxygenase , nitric oxide synthase , tumor necrosis factor alpha , chemistry , nf κb , sulforaphane , interleukin , in vitro , nitric oxide , iκbα , pharmacology , microbiology and biotechnology , biochemistry , biology , heme , cytokine , immunology , enzyme , organic chemistry
In this study, the underlying mechanisms of the potential anti‐inflammatory properties of allyl‐isothiocyanate (AITC) were analysed in vitro and in vivo . Murine RAW264.7 macrophages stimulated with lipopolysaccharide (LPS) were supplemented with increasing concentrations of AITC. In addition, C57BL/6 mice ( n = 10 per group) were fed a pro‐inflammatory high‐fat diet and AITC was administered orally via gavage for 7 days. Biomarkers of inflammation were determined both in cultured cells and in mice. AITC significantly decreased tumour necrosis factor α mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro‐inflammatory markers including interleukin‐1β and inducible nitric oxide synthase were down‐regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF‐κB. Importantly, our data indicate that AITC significantly attenuated microRNA‐155 levels in LPS‐stimulated RAW264.7 macrophages in a dose‐dependent manner. The anti‐inflammatory effects of AITC were accompanied by an increase in Nrf2 nuclear translocation and consequently by an increase of mRNA and protein levels of the Nrf2 target gene heme‐oxygenase 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down‐regulating inflammation in LPS‐stimulated macrophages. A significant increase in nuclear Nrf2 and heme‐oxygenase 1 gene expression and only a moderate down‐regulation of interleukin‐1β and microRNA‐155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti‐inflammatory activity in cultured macrophages in vitro but has only little anti‐inflammatory activity in mice in vivo .