The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
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
Open accessAbstract
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 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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Metadata
- Authors
- Fan, J., Frey, R. S., Rahman, A., & Malik, A. B.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Fan, Jie
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 277
- Issue
- 5
- Pages
- 3404-3411
- ISSN
- 0021-9258 (ISSN-L)
- 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
- hybrid
- doi.org
- 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 (medical) › 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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