A specific p47phox        -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

Dang, Pham My-Chan; Stensballe, Allan; Boussetta, Tarek; Raad, Houssam; Dewas, Cédric; Kroviarski, Yolande; Hayem, Gilles; Jensen, Ole N.; Gougerot-Pocidalo, M A; El-Benna, Jamel

doi:10.1172/jci27544

Cited by 288 publications

(299 citation statements)

References 61 publications

(59 reference statements)

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“…The phosphorylation of p47 phox and the activation of Rac1 plays an essential role in the assembly of the oxidase complex. Pro-inflammatory cytokines (TNF-a, GM-CSF, and G-CSF), LPS, phorbol-12-myristate-13-acetate (PMA), and N-formylmethionyl leucyl phenylalanine (fMLP) are well-known kinase inducers of p47 phox phosphorylation (81,83,88,93,241). p47…”

Section: A Nadph Oxidase-derived Ros In Inflammationmentioning

confidence: 99%

“…phox is phosphorylated at multiple serine residues at C-terminus and is targeted by multiple pathways, such as protein kinase C-d, -b and -f, protein kinase A, Akt, ERK1/2, and p38 mitogen-activated protein kinase (62,82,83,87,94,106). The phosphorylation of p47 phox relieves it from auto-inhibitory conformation, which subsequently leads to unmasking of N-terminal SH3 domain and enabling binding to the proline-rich target in the C-terminus of p22 phox .…”

Section: A Nadph Oxidase-derived Ros In Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Reactive Oxygen Species in Inflammation and Tissue Injury

Mittal

Siddiqui

Tran

et al. 2014

Antioxidants & Redox Signaling

3,266

2,424

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Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126-1167.

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Section: A Nadph Oxidase-derived Ros In Inflammationmentioning

confidence: 99%

Section: A Nadph Oxidase-derived Ros In Inflammationmentioning

confidence: 99%

Reactive Oxygen Species in Inflammation and Tissue Injury

Mittal

Siddiqui

Tran

et al. 2014

Antioxidants & Redox Signaling

3,266

2,424

View full text Add to dashboard Cite

show abstract

“…We next analyzed signaling pathways controlling activation of NADPH oxidase in As 2 O 3 -treated macrophages by studying involvement of MAPKs which can regulate NADPH oxidase activity in phagocytes (21). Neither the ERK pathway inhibitor PD98059 nor the JNK inhibitor D-JNKI1 could prevent superoxide production in macrophages treated with iAs for 72 h (data not shown).…”

Section: As 2 O 3 -Induced Nadph Oxidase Activation Involves P38 Kinasementioning

confidence: 99%

“…Invalidation of the NCF1 gene, which encodes p47 phox , or inhibition of serine p47 phox phosphorylation, correlates with reduced superoxide production (19,20). Several kinases have been demonstrated to increase phosphorylation of p47 phox serine residues, including the ERK (ERK1/2) and p38 kinase (18,21). Once produced, superoxides are released either outside or inside the cells and then rapidly converted into hydrogen peroxide (H 2 O 2 ) (17).…”

Section: Norganic Arsenic (Ias)mentioning

confidence: 99%

Inorganic Arsenic Activates Reduced NADPH Oxidase in Human Primary Macrophages through a Rho Kinase/p38 Kinase Pathway

Lemarié

Bourdonnay

Morzadec

et al. 2008

The Journal of Immunology

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Inorganic arsenic is an immunotoxic environmental contaminant to which millions of humans are chronically exposed. We recently demonstrated that human primary macrophages constituted a critical target for arsenic trioxide (As2O3), an inorganic trivalent form. To specify the effects of arsenic on macrophage phenotype, we investigated in the present study whether As2O3 could regulate the activity of NADPH oxidase, a major superoxide-generating enzymatic system in human phagocytes. Our results show that superoxide levels were significantly increased in a time-dependent manner in blood monocyte-derived macrophages treated with 1 μM As2O3 for 72 h. Concomitantly, As2O3 induced phosphorylation and membrane translocation of the NADPH oxidase subunit p47phox and it also increased translocation of Rac1 and p67phox. Apocynin, a selective inhibitor of NADPH oxidases, prevented both p47phox translocation and superoxide production. NADPH oxidase activation was preceded by phosphorylation of p38-kinase in As2O3-treated macrophages. The p38-kinase inhibitor SB-203580 prevented phosphorylation and translocation of p47phox and subsequent superoxide production. Pretreatment of macrophages with the Rho-kinase inhibitor Y-27632 was found to mimic inhibitory effects of SB-203580 and to prevent As2O3-induced phosphorylation of p38 kinase. Treatment with As2O3 also resulted in an increased secretion of the proinflammatory chemokine CCL18 that was fully inhibited by both apocynin and SB-203580. Taken together, our results demonstrate that As2O3 induced a marked activation of NADPH oxidase in human macrophages, likely through stimulation of a Rho-kinase/p38-kinase pathway, and which may contribute to some of the deleterious effects of inorganic arsenic on macrophage phenotype.

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“…In immune scenarios, ROS are produced and secreted by activated neutrophils and macrophages via NADPH oxidation at inflammation sites, which often provide oxidative microenvironment for T cells (Fialkow et al, 1993;Dang et al, 2006). In addition, macrophage derived inflammatory cytokines such as tumor necrosis factor (TNF)-a induces ROS generation in target cells (Sparwasser et al, 1997;Odaka et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

SOCS1 protects protein tyrosine phosphatases by thioredoxin upregulation and attenuates Jaks to suppress ROS-mediated apoptosis

Hur

2009

Oncogene

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Suppressors of cytokine signaling (SOCS) are negative regulators of cytokine-induced signal transduction, which play multiple roles in cell growth, differentiation and apoptosis. In this study, the regulatory role of SOCS in oxidative stress-induced apoptosis was investigated. In Jurkat T cells and mouse splenocytes, we have found that SOCS1 is induced in response to tumor necrosis factor-a or H 2 O 2 , concomitant with the activation of Jaks which act as important mediators of reactive oxygen species (ROS)-induced apoptosis upstream of p38 mitogenactivated protein kinase. Using SOCS1 overexpressing or knockdown Jurkat T-cell systems we clearly demonstrate that, SOCS1 inhibits the ROS-mediated apoptosis. The antiapoptotic action of SOCS1 was exerted not only by suppressing Jaks, but also by sustaining protein tyrosine phosphatase (PTP) activities. Notably, SOCS1-transduced cells displayed increase in thioredoxin levels and decrease in ROS generation induced by oxidative stress. In addition, the Jak-inhibiting and PTP-sustaining effect of SOCS1 was significantly reduced on thioredoxin ablation. Moreover, coimmunoprecipitation data revealed molecular interaction of SHP1 or CD45 with thioredoxin, which was promoted in SOCS1-transfected cells. Together, our data strongly suggest that both the protection of PTPs by thioredoxin from ROS attack and the attenuation of Jaks account for the antiapoptotic function of SOCS1 in immune cells under oxidative stress.

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A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

Cited by 288 publications

References 61 publications

Reactive Oxygen Species in Inflammation and Tissue Injury

Reactive Oxygen Species in Inflammation and Tissue Injury

Inorganic Arsenic Activates Reduced NADPH Oxidase in Human Primary Macrophages through a Rho Kinase/p38 Kinase Pathway

SOCS1 protects protein tyrosine phosphatases by thioredoxin upregulation and attenuates Jaks to suppress ROS-mediated apoptosis

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