title: Anti-inflammatory potential of allyl-isothiocyanate--role of Nrf2, NF-(κ) B and microRNA-155.
abstract: 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.
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany. wagner@molecularnutrition.uni-kiel.de
authors.forename: Anika Eva
authors.initials: AE
authors.lastname: Wagner
authors.forename: Christine
authors.initials: C
authors.lastname: Boesch-Saadatmandi
authors.forename: Janina
authors.initials: J
authors.lastname: Dose
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schultheiss
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017879:Isothiocyanates / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D017931:DNA Primers; D017879:Isothiocyanates; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C004471:allyl isothiocyanate