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Elevated Mitochondr...
Elevated Mitochondrial Reactive Oxygen Species and Cellular Redox Imbalance in Human NADPH-Oxidase-Deficient Phagocytes
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- Sundqvist, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Christenson, Karin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för odontologi,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Odontology
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- Björnsdottir, Halla (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för odontologi,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Odontology
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- Osla, Veronica (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Karlsson, Anna, 1967 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Dahlgren, Claes, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Speert, D. P. (author)
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- Fasth, Anders, 1945 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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Brown, K. L. (author)
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- Bylund, Johan, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för odontologi,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Odontology,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- 2017-12-21
- 2017
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Abstract
Subject headings
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- Chronic granulomatous disease (CGD) is caused by mutations in genes that encode the NADPH-oxidase and result in a failure of phagocytic cells to produce reactive oxygen species (ROS) via this enzyme system. Patients with CGD are highly susceptible to infections and often suffer from inflammatory disorders; the latter occurs in the absence of infection and correlates with the spontaneous production of inflammatory cytokines. This clinical feature suggests that NADPH-oxidase-derived ROS are not required for, or may even suppress, inflammatory processes. Experimental evidence, however, implies that ROS are in fact required for inflammatory cytokine production. By using a myeloid cell line devoid of a functional NADPH-oxidase and primary CGD cells, we analyzed intracellular oxidants, signs of oxidative stress, and inflammatory cytokine production. Herein, we demonstrate that phagocytes lacking a functional NADPH-oxidase, namely primary CGD phagocytes and a gp91phox-deficient cell line, display elevated levels of ROS derived from mitochondria. Accordingly, these cells, despite lacking the major source of cellular ROS, display clear signs of oxidative stress, including an induced expression of antioxidants and altered oxidation of cell surface thiols. These observed changes in redox state were not due to abnormalities in mitochondrial mass or membrane integrity. Finally, we demonstrate that increased mitochondrial ROS enhanced phosphorylation of ERK1/2, and induced production of IL8, findings that correlate with previous observations of increased MAPK activation and inflammatory cytokine production in CGD cells. Our data show that elevated baseline levels of mitochondria-derived oxidants lead to the counter-intuitive observation that CGD phagocytes are under oxidative stress and have enhanced MAPK signaling, which may contribute to the elevated basal production of inflammatory cytokines and the sterile inflammatory manifestations in CGD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- chronic granulomatous disease
- oxidative stress
- reactive oxygen species
- inflammation
- cytokine
- chronic granulomatous-disease
- controls phagosomal ph
- hydrogen-peroxide
- gene-expression
- dendritic cells
- neutrophils
- activation
- apoptosis
- line
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Sundqvist, Marti ...
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Christenson, Kar ...
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Björnsdottir, Ha ...
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Osla, Veronica
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Karlsson, Anna, ...
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Dahlgren, Claes, ...
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Speert, D. P.
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Fasth, Anders, 1 ...
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Brown, K. L.
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Bylund, Johan, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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Frontiers in Imm ...
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University of Gothenburg