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ToolsRushworth, SA, Macewan, DJ and O'Connell, MA (2008) Lipopolysaccharide induced expression of NQO1 and HO-1 protects against excessive inflammatory responses. The Journal of Immunology, 181 (10). pp. 6730-6737. ISSN 0022-1767
Full text not available from this repository. (Request a copy)Abstract
Monocytes play a central role in the immunopathological effects of sepsis. This role is mediated by production of the cytokines tumor necrosis factor α (TNF) and interleukin-1β (IL-1β). The transcription factor NF-E2-related factor 2 (Nrf2) regulates innate immune responses in various experimental disease models. Presently, the role of Nrf2-regulated genes in lipopolysaccharide (LPS)-treated human monocytes is not well defined. Here we show that Nrf2 mediates a significant regulation of LPS-induced inflammatory responses. Analysis of Nrf2-regulated gene expression in human monocytes showed that LPS induced the expression of the phase II detoxification gene NAD(P)H:quinone oxidoreductase 1 (NQO1). Furthermore, NQO1 mRNA or protein expression in response to LPS was regulated by Nrf2. Silencing Nrf2 expression in human monocytes inhibited LPS-induced NQO1 expression, however by contrast, it significantly increased TNF and IL-1β production. Silencing expression of NQO1 alone, or in combination with heme oxygenase-1 (HO-1) silencing, markedly increased LPS-induced TNF and IL-1β expression. Additionally, overexpression of NQO1 and/or HO-1 inhibited LPS-induced TNF and IL-1β expression. These results show for the first time that LPS induces NQO1 and HO-1 expression in human monocytes via Nrf2 to modulate their inflammatory responsiveness, thus providing novel potential therapeutic strategies for the treatment of sepsis.
| Item Type: | Article |
|---|---|
| Depositing User: | Rachel Smith |
| Date Deposited: | 05 Apr 2011 15:58 |
| Last Modified: | 23 Aug 2011 12:06 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/28110 |
| DOI: |
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