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Göteborgs universitets publikationer

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kappa B

Författare och institution:
Johan Bylund (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); K. L. Macdonald (-); Kelly Brown (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); P. Mydel (-); Vincent Collins (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); R. E. Hancock (-); D. P. Speert (-)
Publicerad i:
Eur J Immunol, 37 ( 4 ) s. 1087-96
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Reactive oxygen species (ROS) generated by the cellular NADPH-oxidase are crucial for phagocytic killing of ingested microbes and have been implicated as signaling molecules in various processes. For example, ROS are thought to be involved in activation of the transcription factor NF-kappaB, central for mediating production of proinflammatory cytokines in response to inflammatory stimuli. Several studies have demonstrated that inhibitors of the NADPH-oxidase interfere with NF-kappaB activation and production of proinflammatory cytokines. Curiously, patients with chronic granulomatous disease (CGD), an immunodeficiency characterized by an inability to produce ROS, are not only predisposed to severe infections, but also frequently develop various inflammatory complications indicative of exaggerated inflammatory responses. Here, we show that human CGD leukocytes display a hyperinflammatory phenotype with increased production of proinflammatory cytokines in response to stimulation with Toll-like receptor agonists. The hyperinflammatory phenotype was also evident in mononuclear cells from CGD mice (gp91(phox) -/-), but not in control cells in the presence of NADPH-oxidase inhibitor diphenyleneiodonium, probably reflecting NADPH-oxidase-independent effects of the inhibitor. Furthermore, we show that the major steps involved in NF-kappaB activation were intact in human CGD cells. These data indicate that ROS were nonessential for activation of NF-kappaB and their production may even attenuate inflammation.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Cells, Cultured, Cytokines/biosynthesis, Female, Granulomatous Disease, Chronic/*immunology/metabolism/*pathology, Humans, Leukocytes/*immunology/metabolism/*pathology, Male, Membrane Glycoproteins/deficiency/genetics, Mice, Mice, Inbred C57BL, NADPH Oxidase/deficiency/genetics, NF-kappa B/*metabolism, Reactive Oxygen Species/*metabolism
Postens nummer:
Posten skapad:
2008-01-04 11:35
Posten ändrad:
2011-01-20 09:58

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