ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Impaired priming and activation of the neutrophil NADPH oxidase in patients with IRAK4 or NEMO deficiency.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Human inborn errors of the phagocyte respiratory burst: Chronic granulomatous disease and beyond.Journal of human immunity · 2026Article
- Blocking MyD88 Signaling Pathway Protects Against Myocardial Ischemia Reperfusion by Inhibiting NOX/ROS Pathway and Enhancing eNOS Activity.International journal of molecular sciences · 2026Article
- In Silico and In Vitro Studies of Anti-Inflammatory, Anti-Oxidative Stress, and Anti-Apoptosis Effect of 7-Octenoic Acid Derived fromInternational journal of molecular sciences · 2025Article
- β-hydroxybutyrate impairs monocyte functionFrontiers in veterinary science · 2022Article
- Immunity toMicrobiology spectrum · 2019Review
- Bacterial lipoproteins and other factors released by Francisella tularensis modulate human neutrophil lifespan: Effects of a TLR1 SNP on apoptosis inhibition.Cellular microbiology · 2018Article
- TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages.BMC pulmonary medicine · 2017Article
- Thrombin-derived host defence peptide modulates neutrophil rolling and migration in vitro and functional response in vivo.Scientific reports · 2017Article
- Macrophage-derived IL-1β enhances monosodium urate crystal-triggered NET formation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Regulation of CYBB Gene Expression in Human Phagocytes by a Distant Upstream NF-κB Binding Site.Journal of cellular biochemistry · 2015Article
- Neutrophils: Between host defence, immune modulation, and tissue injury.PLoS pathogens · 2015Review
- The multifaceted functions of neutrophils.Annual review of pathology · 2014Review
- Neutropenia in primary immunodeficiency.Current opinion in hematology · 2013Review
- The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils.Nature immunology · 2012Article
- TLR signaling and effector functions are intact in XLA neutrophils.Clinical immunology (Orlando, Fla.) · 2010Article
- NADPH oxidase-dependent reactive oxygen species mediate amplified TLR4 signaling and sepsis-induced mortality in Nrf2-deficient mice.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Inhibition of IkappaB kinase-beta protects dopamine neurons against lipopolysaccharide-induced neurotoxicity.The Journal of pharmacology and experimental therapeutics · 2010Article
- IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species generation in macrophages by inducing NOX-1 transcription and Rac1 activation and suppressing the expression of antioxidative enzymes.The Journal of biological chemistry · 2009Article
- Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading pathogens.BioFactors (Oxford, England)Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
The NADPH oxidase (NOX), an oligomeric enzyme, plays a key role in polymorphonuclear neutrophil (PMN)-mediated host defense by producing cytotoxic superoxide anion (O(2)( )). Whereas in vitro and biochemical studies have examined the assembly and activation of this important host immune defense system, few studies have examined the function of NOX in human patients with primary immunodeficiency other than chronic granulomatous disease. We studied the activation of NOX in PMN from patients with two distinct immunodeficiencies, IL-1R-associated kinase (IRAK)4 deficiency and NF-kappaB essential modulator (NEMO or IkappaB kinase gamma) deficiency. We observed impaired O(2)( ) generation by LPS-treated and fMLP-activated IRAK4-deficient PMN that correlated with decreased phosphorylation of p47(phox) and subnormal translocation of p47(phox), p67(phox), Rac2, and gp91(phox)/Nox2 to the membranes indicating that TLR4 signaling to the NOX activation pathway requires IRAK4. NEMO-deficient PMN generated significantly less O(2)( ) in response to LPS-primed fMLP and translocated less p67(phox) than normal PMN, although p47(phox) and Rac2 translocation were normal. Generally, responses of NEMO-deficient cells were intermediate between IRAK4-deficient cells and normal cells. Decreased LPS- and fMLP-induced phosphorylation of p38 MAPK in both IRAK4- and NEMO-deficient PMN implicates additional signal transduction pathways in regulating PMN activation by LPS and fMLP. Decreased activation of NOX may contribute to the increased risk of infection seen in patients with IRAK4 and NEMO deficiency.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.