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Anti-inflammatory potential of allyl-isothiocyanate-role of Nrf2, NFkB and microRNA-155

Lookup NU author(s): Dr Christine Bosch-Saadatmandi

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Abstract

In the present 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 tumor 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 NO synthase were down-regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NFκB. 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 relatively little anti-inflammatory activity in mice in vivo.


Publication metadata

Author(s): Wagner AE, Boesch-Saadatmandi C, Dose J, Schultheiss G, Rimbach G

Publication type: Article

Journal: Journal of Cellular and Molecular Medicine

Year: 2012

Volume: 16

Issue: 4

Pages: 836-843

Print publication date: 22/06/2011

ISSN (print): 1582-1838

ISSN (electronic): 1582-4934

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1582-4934.2011.01367.x

DOI: 10.1111/j.1582-4934.2011.01367.x


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