Implication of NADPH Oxidases in the Early Inflammation Process Generated by Cystic Fibrosis Cells

Pongnimitprasert, Nushjira; Hurtado, Margarita; Lamari, F.; Benna, Jamel El; Dupuy, Corinne; Fay, Michèle; Foglietti, Marie-José; Bernard, Maguy; Gougerot‐Pocidalo, Marie‐Anne; Braut-Boucher, F.

doi:10.5402/2012/481432

Cited by 9 publications

(9 citation statements)

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“…Based on the proposed roles of DUOX1/DUOX2 in mucosal host defence by providing extracellular H 2 O 2 to support LPO‐mediated production of HOSCN, it has been speculated that genetic diseases associated with increased lung injury and infection, such as cystic fibrosis, may be related to defects in this host defence system. Indeed, defects in the cystic fibrosis transmembrane conductance regulator gene that cause cystic fibrosis have been associated with impaired transepithelial SCN − transport, thus resulting in reduced DUOX–LPO‐dependent mucosal host defence (Conner et al ., ; Moskwa et al ., ), although they do not appear to significantly affect DUOX1/DUOX2 expression (Pongnimitprasert et al ., ; van der Vliet et al ., unpubl. data).…”

Section: Duox In Disease Pathologymentioning

confidence: 99%

Dual oxidase: a novel therapeutic target in allergic disease

Vliet

Danyal

Heppner

2018

British J Pharmacology

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NADPH oxidases (NOXs) represent a family of enzymes that mediate regulated cellular production of reactive oxygen species (ROS) and play various functional roles in physiology. Among the NOX family, the dual oxidases DUOX1 and DUOX2 are prominently expressed in epithelial cell types at mucosal surfaces and have therefore been considered to have important roles in innate host defence pathways. Recent studies have revealed important insights into the host defence mechanisms of DUOX enzymes, which control innate immune response pathways in response to either microbial or allergic triggers. In this review, we discuss the current level of understanding with respect to the biological role(s) of DUOX enzymes and the unique role of DUOX1 in mediating innate immune responses to epithelial injury and allergens and in the development of allergic disease. These novel findings highlight DUOX1 as an attractive therapeutic target, and opportunities for the development of selective inhibitor strategies will be discussed. AbbreviationsCPZ, chlorpromazine; DPI, diphenylene iodonium; DUOX, dual oxidase; DUOXA, dual oxidase maturation factor; EGFR, EGF receptor; ER, endoplasmic reticulum; HDM, house dust mite; ILC2, type 2 innate lymphoid cell; LPO, lactoperoxidase; MPO, myeloperoxidase; NOX, NADPH oxidase; NOXA, NOX activator; PDB, protein database; PHD, peroxidase homology domain; ROS, reactive oxygen species; TK, tyrosine kinase; TLR, toll-like receptor; TPO, thyroperoxidase; TRX, thioredoxin IntroductionThe concept of oxidative stress has been widely embraced as a major factor in disease pathology and has fuelled a billion dollar industry based on antioxidant dietary supplements. However, clinical studies using antioxidant supplementation strategies have generally been unsuccessful in attenuating disease risk or progression, and antioxidant supplementation was in some cases found to even worsen pathological outcomes (Ghezzi et al., 2017). This lack of success likely relates to the flawed concept of oxidative stress as a pharmacological target. First, oxidative stress can be brought about by a range of ROS (the commonly used acronym to define this group of reactive metabolites), which can originate from external sources (e.g. environmental pollution and metabolism of xenobiotics) or be generated endogenously by various enzymatic systems, in some cases in a regulated and deliberate fashion to serve important biological functions [e.g. by activation of NADPH oxidases (NOXs)]. Therefore, generic non-selective approaches that indiscriminately suppress ROS may not have the desired outcome. A second flaw with such generic antioxidant approaches is the fact that ROS represent a diverse group of reactive metabolites that each have unique (bio)chemical properties, and it is often unclear to what extent antioxidant supplements counter the action of individual ROS species. To clarify this, it is helpful to distinguish primary from secondary ROS, with primary ROS representing the initial products of (enzymatic) O 2 reduction [i.e. superoxi...

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Section: Duox In Disease Pathologymentioning

confidence: 99%

Dual oxidase: a novel therapeutic target in allergic disease

Vliet

Danyal

Heppner

2018

British J Pharmacology

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“…Protein kinases C can also be activated by oxidative stress [ 78 ]. Moreover, oxidative stress produces a wide range of DNA mutations [ 79 ] by exogenous oxidative stimuli like high levels of alkylating agents [ 80 ], radiation [ 81 ], antioxidant depletion [ 82 ] or during inflammation process [ 83 ].…”

Section: Biologic Performances Of Obesitymentioning

confidence: 99%

Obesity and colorectal cancer: molecular features of adipose tissue

2016

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The huge part of population in developed countries is overweight or obese. Obesity is often determined by body mass index (BMI) but new accurate methods and ratios have recently appeared to measure body fat or fat located in the intestines. Early diagnosis of obesity is crucial since it is considered an increasing colorectal cancer risk factor. On the one hand, colorectal cancer has been strongly associated with lifestyle factors. A diet rich in red and processed meats may increase colorectal cancer risk; however, high-fiber diets (grains, cereals and fruits) have been associated with a decreased risk of colorectal cancer. Other life-style factors associated with obesity that also increase colorectal cancer risk are physical inactivity, smoking and high alcohol intake. Cutting-edge studies reported that high-risk transformation ability of adipose tissue is due to production of different pro-inflammatory cytokines like IL-8, IL-6 or IL-2 and other enzymes like lactate dehydrogenase (LDH) and tumour necrosis factor alpha (TNFα). Furthermore, oxidative stress produces fatty-acid peroxidation whose metabolites possess very high toxicities and mutagenic properties. 4-hydroxy-2-nonenal (4-HNE) is an active compounds that upregulates prostaglandin E2 which is directly associated with high proliferative colorectal cancer. Moreover, 4-HNE deregulates cell proliferation, cell survival, differentiation, autophagy, senescence, apoptosis and necrosis via mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PIK3CA)—AKT and protein kinase C pathways. Other product of lipid peroxidation is malondialdehyde (MDA) being able to regulate insulin through WNT-pathway as well as having demonstrated its mutagenic capability. Accumulation of point mutation enables genomic evolution of colorectal cancer described in the model of Fearon and Vogelstein. In this review, we will summarize different determination methods and techniques to assess a truthfully diagnosis and we will explain some of the capabilities that performs adipocytes as the largest endocrine organ.

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“…NOX2, which is highly expressed in inflammatory cells, plays an essential role in non-specific host defence against pathogens and is defective in the genetic disorder chronic granulomatous disease [9]. The other NOX isoforms, named NOX1-4 and DUOX1/2, have been described in several lung 66 C Trocme et al cell types and are associated with lung pathological situations [10][11][12][13][14][15][16][17][18][19]. Some studies indicate that NOX enzymes contribute to the pathogenesis of COPD.…”

Section: Introductionmentioning

confidence: 99%

Macrophage‐specific NOX2 contributes to the development of lung emphysema through modulation of SIRT1/MMP‐9 pathways

Trocmé

Deffert

Cachat

et al. 2014

The Journal of Pathology

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Reactive oxygen species (ROS) participate in the pathogenesis of emphysema. Among ROS-producing enzymes, NOX NADPH oxidases are thought to be responsible for tissue injury associated with several lung pathologies. To determine whether NOX2 and/or NOX1 participate in the development of emphysema, their expression patterns were first studied by immunohistochemistry in the lungs of emphysematous patients. Subsequently, we investigated their contribution to elastase-induced emphysema using NOX2- and NOX1-deficient mice. In human lung, NOX2 was mainly detected in macrophages of control and emphysematous lungs, while NOX1 was expressed in alveolar epithelium and bronchial cells. We observed an elevated number of NOX2-positive cells in human emphysematous lungs, as well as increased NOX2 and NOX1 mRNA expression in mouse lungs following elastase exposure. Elastase-induced alveolar airspace enlargement and elastin degradation were prevented in NOX2-deficient mice, but not in NOX1-deficient mice. This protection was independent of inflammation and correlated with reduced ROS production. Concomitantly, an elevation of sirtuin 1 (SIRT1) level and a decrease of matrix metalloproteinase-9 (MMP-9) expression and activity were observed in alveolar macrophages and neutrophils. We addressed the specific role of macrophage-restricted functional NOX2 in elastase-induced lung emphysema using Ncf1 mutant mice and Ncf1 macrophage rescue mice (Ncf1 mutant mice with transgenic expression of Ncf1 only in CD68-positive mononuclear phagocytes; the MN mouse). Compared to WT mice, the lack of functional NOX2 led to decreased elastase-induced ROS production and protected against emphysema. In contrast, ROS production was restored specifically in macrophages from Ncf1 rescue mice and contributes to emphysema. Taken together, our results demonstrate that NOX2 is involved in the pathogenesis of human emphysema and macrophage-specific NOX2 participates in elastase-induced emphysema through the involvement of SIRT1/MMP-9 pathways in mice.

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Implication of NADPH Oxidases in the Early Inflammation Process Generated by Cystic Fibrosis Cells

Cited by 9 publications

References 45 publications

Dual oxidase: a novel therapeutic target in allergic disease

Dual oxidase: a novel therapeutic target in allergic disease

Obesity and colorectal cancer: molecular features of adipose tissue

Macrophage‐specific NOX2 contributes to the development of lung emphysema through modulation of SIRT1/MMP‐9 pathways

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