Regulation of innate immunity by NADPH oxidase

Segal, Brahm H.; Grimm, Melissa; Khan, Atiya; Han, Wei; Blackwell, Timothy S.

doi:10.1016/j.freeradbiomed.2012.04.022

Cited by 126 publications

(91 citation statements)

References 129 publications

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“…Further studies are required to delineate the relative importance of ROI-mediated fungal damage versus NETosis in promoting Aspergillus clearance. In addition to its host defense function, we and others have found that NADPH oxidase can modulate oxidant-sensitive pathways that limit lung inflammation and injury following challenge with both microbial products and direct caustic insult (14,15,30,(65)(66)(67)(68). Delineating…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis

et al. 2014

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f NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates. Aspergillus species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in Aspergillus fumigatus pneumonia. Oropharyngeal instillation of live Aspergillus hyphae induced neutrophilic pneumonitis in both wildtype and NADPH oxidase-deficient (p47 phox؊/؊ ) mice which had resolved in wild-type mice by day 5 but progressed in p47 phox؊/؊ mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47 phox؊/؊ mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase in vivo and ex vivo. In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of Aspergillus hyphae and generation of NETs in vivo. We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance.

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Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis

et al. 2014

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“…They exist as seven distinct isoforms (NOX1-NOX5 and the dual oxidases DUOX1 and DUOX2), structurally composed of a core catalytic subunit and various regulatory subunits (p40 phox , p47 phox , p67 phox , p22 phox , NOXA1, NOXO1, DUOXA1, and DUOXA2) determining spatial organization, membrane location, subcellular expression, and activation of the enzyme (Drummond et al, 2011;Segal et al, 2012). Activation of NOX catalyzes the transfer of electrons from cytosolic NADPH to molecular oxygen to form O 2 .-.…”

Section: The Family Of Rosmentioning

confidence: 99%

“…For NOX4 and DUOX1-2, the primary ROS produced is H 2 O 2 instead of O 2 .-. ROS produced by NOXs regulate multiple cellular (e.g., differentiation, proliferation, and migration) and physiological (e.g., vascular tone, oxygen sensing) processes (Drummond et al, 2011;Segal et al, 2012). Excess ROS production and oxidative stress occurs when overactivation of NOX occurs in response to stimuli as diverse as hyperglycemia, angiotensin II, growth factors, hormones (Schramm et al, 2012), and most significantly inflammatory cytokines such as interleukin (IL)-1β (Ginnan et al, 2013) and TNFα (Frey et al, 2002).…”

Section: The Family Of Rosmentioning

confidence: 99%

The role of oxidative stress during inflammatory processes

Lugrin¹,

Rosenblatt‐Velin

Parapanov³

et al. 2013

Biological Chemistry

580

393

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Abstract:The production of various reactive oxidant species in excess of endogenous antioxidant defense mechanisms promotes the development of a state of oxidative stress, with significant biological consequences. In recent years, evidence has emerged that oxidative stress plays a crucial role in the development and perpetuation of inflammation, and thus contributes to the pathophysiology of a number of debilitating illnesses, such as cardiovascular diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all stages of the inflammatory response, including the release by damaged tissues of molecules acting as endogenous danger signals, their sensing by innate immune receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the activation of signaling pathways initiating the adaptive cellular response to such signals. In this article, after summarizing the basic aspects of redox biology and inflammation, we review in detail the current knowledge on the fundamental connections between oxidative stress and inflammatory processes, with a special emphasis on the danger molecule highmobility group box-1, the TLRs, the NLRP-3 receptor, and the inflammasome, as well as the transcription factor nuclear factor-κB.

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“…The role of inflammation on oxidative stress can be explained in two ways. First, inflammation directly increases the level of hydrogen peroxide in thyroid epithelial cells, and second, it activates NOX enzyme in T and B lymphocytes, which increases ROS production (22,23). In fact, the Th1 cytokines (predominant in HT) are known to decrease DUOX and thus H 2 O 2 production but to increase NOX2 (without affecting NOX4) (24).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

The relationship between oxidative stress and autoimmunity in Hashimoto's thyroiditis

Ateş

Yılmaz

Altay

et al. 2015

European Journal of Endocrinology

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Objective: We have aimed to study the relation between Hashimoto's thyroiditis (HT) and thyroid autoantibodies and oxidative stress parameters in euthyroid, subclinical and overt hypothyroid stages. Design and methods: A total of 124 patients were included in the study; 93 of whom were newly diagnosed with HT (31 patients in each of the euthyroid, subclinical hypothyroid and overt hypothyroid subgroups), aged over 18 and had not received any prior treatment and 31 of whom were healthy volunteers. Results: Total oxidant status (TOS) and oxidative stress index (OSI) levels were higher, and total antioxidant status (TAS) and total thiol and arylesterase levels were lower in the overt hypothyroid group compared to other groups. TOS and OSI levels increased, and TAS levels decreased significantly in each phase from euthyroid, subclinical hypothyroid, to overt hypothyroid subgroups among HT patients. There was a negative correlation between TAS, log (paraoxonase1) and paraoxonase1/HDL and anti-thyroid peroxidase and a negative correlation between anti-thyroglobulin and total thiol. It was also determined that overt hypothroidism was an individual predictor that effects all of the oxidative stress parameters, but not total thiol, levels. Conclusion: Our results suggest that oxidative stress increases continuously during the development of subclinical hypothyroidism and overt hypothyroidism in patients with HT. To determine whether this is a cause or result, randomized, controlled trials that study the effect of antioxidant treatment on the development of overt hypothyroidism and its consequences, e.g., increase in total cholesterol levels, may be performed in euthyroid and/or subclinical hypothyroid patients with HT.

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Regulation of innate immunity by NADPH oxidase

Cited by 126 publications

References 129 publications

NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis

NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis

The role of oxidative stress during inflammatory processes

The relationship between oxidative stress and autoimmunity in Hashimoto's thyroiditis

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