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Cited by 130Neutrophil, Myeloperoxidase and Oxidative MechanismsNF-κB Signaling PathwaysNitric Oxide and Endothelin Effects

Role of Neutrophil NADPH Oxidase in the Mechanism of Tumor Necrosis Factor-α-induced NF-κB Activation and Intercellular Adhesion Molecule-1 Expression in Endothelial Cells

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Fan, Jie, Frey, Randall S., Rahman, Arshad, Malik, Asrar B.·2002·Journal of Biological Chemistry
DOI 10.1074/jbc.m110054200
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Abstract

In this study, we explored a novel function of polymorphonuclear neutrophils (PMN) NAD(P)H oxidase in the mechanism of tumor necrosis factor-alpha (TNFalpha)-induced NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. Studies were made in mice lacking the p47(phox) subunit of NAD(P)H oxidase as well as in cultured mouse lung vascular endothelial cells (MLVEC) from these mice. In response to TNFalpha challenge, NF-kappaB activation and ICAM-1 expression were significantly attenuated in lungs of p47(phox)(-/-) mice as compared with wild-type (WT) mice. The attenuated NF-kappaB activation in p47(phox)(-/-) mice was secondary to inhibition of NIK activity and subsequent IkappaBalpha degradation. Induction of neutropenia using anti-PMN serum prevented the initial TNFalpha-induced NF-kappaB activation and ICAM-1 expression in WT mice, indicating the involvement of PMN NAD(P)H oxidase in signaling these responses. Moreover, the responses were restored upon repletion with PMN obtained from WT mice but not with PMN from p47(phox)(-/-) mice. These findings were recapitulated in MLVEC co-cultured with PMN, suggesting that NF-kappaB activation and resultant ICAM-1 expression in endothelial cells occurred secondary to oxidants generated by the PMN NAD(P)H oxidase complex. The functional relevance of the PMN NAD(P)H oxidase in mediating TNFalpha-induced ICAM-1-dependent endothelial adhesivity was evident by markedly reduced adhesion of p47(phox)(-/-) PMN in co-culture experiments. Thus, oxidant signaling by the PMN NAD(P)H oxidase complex is an important determinant of TNFalpha-induced NF-kappaB activation and ICAM-1 expression in endothelial cells.

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  • A large number of cytokines and hormones induce NOX2 expression, including angiotensin II, thrombin, and TNF-α.

    “A large number of cytokines and hormones have been shown to induce NOX2 expression, including angiotensin II (658, 714, 802), thrombin (725), and TNF-α (275, 964).”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [275]

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Authors
Fan, J., Frey, R. S., Rahman, A., & Malik, A. B.
Affiliations
University of Illinois Chicago (US)
Corresponding author
Fan, Jie
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-02
Volume
277
Issue
5
Pages
3404-3411
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m110054200
OpenAlex
W1966454841
Cited by
130
References
43
Citations by year
2026: 1 · 2024: 4 · 2022: 1 · 2021: 6 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 5
FWCI
3.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (T32 HL-07829, P01HL060678, HL-45638, HL 27016, HL 60678, R01HL045638, T32HL007829)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
neutrophil NADPH oxidase, p47phox, TNF-α, NF-κB activation, ICAM-1 expression, endothelial cells, NIK, IκBα degradation, neutrophils, oxidant signaling, neutrophil-endothelial cell adhesion, neutropenia
MeSH terms
NF-KappaB Inhibitor alpha, Animals, DNA-Binding Proteins, Endothelium, Vascular, Gene Expression Regulation, Lung, Mice, Inbred C57BL, Models, Biological, Neutrophils, Nuclear Proteins, Phosphoproteins, Pulmonary Circulation, Tumor Necrosis Factor-alpha, Blotting, Northern, NF-kappa B, Mice, Knockout, Intercellular Adhesion Molecule-1, NADPH Oxidases, I-kappa B Proteins, Mice

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