Cited by 216Genomics, phytochemicals, and oxidative stressHeme Oxygenase-1 and Carbon MonoxideImmune Response and Inflammation

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Lipopolysaccharide-Induced Expression of NAD(P)H:Quinone Oxidoreductase 1 and Heme Oxygenase-1 Protects against Excessive Inflammatory Responses in Human Monocytes

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Rushworth, Stuart A., MacEwan, David J., O’Connell, Maria A.·2008·The Journal of Immunology

DOI 10.4049/jimmunol.181.10.6730PMC PMC2923058

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Abstract

Monocytes play a central role in the immunopathological effects of sepsis. This role is mediated by production of the cytokines TNF-α and 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 LPS-treated human monocytes is not well defined. Herein 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, in 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.

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Authors: Rushworth, S. A., MacEwan, D. J., & O’Connell, M. A.
Affiliations: University of East Anglia (GB)
School of Chemical Sciences and Pharmacy, University of East Anglia , Norwich,
ORCID: Rushworth, Stuart A.
MacEwan, David J.
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2008-11
Volume: 181
Issue: 10
Pages: 6730-6737
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.181.10.6730
PMC: PMC2923058
OpenAlex: W2105691693
Cited by: 215
References: 51
Citations by year: 2026: 7 · 2025: 6 · 2024: 12 · 2023: 8 · 2022: 14 · 2021: 12 · 2020: 18 · 2019: 11 · 2018: 8 · 2017: 14 · 2016: 8 · 2015: 16 · 2014: 17 · 2013: 13 · 2012: 11
FWCI: 5.49
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders: University of East Anglia
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: lipopolysaccharide, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, Nrf2, human monocytes, sepsis, inflammation, TNF-α, IL-1β, innate immunity
MeSH terms: Cell Line, Gene Expression Regulation, Humans, Inflammation, Lipopolysaccharides, Monocytes, RNA, Messenger, Tumor Necrosis Factor-alpha, Gene Expression, NAD(P)H Dehydrogenase (Quinone), Reactive Oxygen Species, Sepsis, Reverse Transcriptase Polymerase Chain Reaction, Gene Silencing, NF-E2-Related Factor 2, Heme Oxygenase-1, Interleukin-1beta

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Lipopolysaccharide-Induced Expression of NAD(P)H:Quinone Oxidoreductase 1 and Heme Oxygenase-1 Protects against Excessive Inflammatory Responses in Human Monocytes

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