Studies on the gene expression of several NADPH oxidase components

Cassatella, Marco A.; Bazzoni, Flavia; Amezaga, Miguel Aste; Rossi, Filippo

doi:10.1042/bst0190063

Cited by 17 publications

(10 citation statements)

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“…cytosolic components of the NADPH oxidase superoxidegenerating system, was strongly enhanced by LPS, as reported (17), and it was increased also by the P2 protein at the 24-h time point (Fig. 1A).…”

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confidence: 60%

“…Although P2 protein did not trigger the production of ROIs by mononuclear phagocytes, regardless of their stage of maturation or activation, it potentiated the oxidative burst capability of monocytes in a manner equivalent to that of LPS or TNF. Interestingly, the mRNA levels of p47-phox, one of the NADPH oxidase components that presumably plays a key role in the mechanism of activation of macrophage respiratory burst (17,22), were also increased in monocytes treated with P2 protein.…”

Section: Discussionmentioning

confidence: 99%

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Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein.

Baron

Constantin

D’Andrea

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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In this study we examined the effect of myelin P2 protein on some proinflammatory functions exerted by human mononuclear phagocytes. Northern blot analysis demonstrated that P2 protein selectively induced in monocytes and macrophages mRNA accumulation of tumor necrosis factor (TNF), interleukin 113 (IL-10), and interleukin 8 (IL-8) in a time-dependent manner. Natural killer stimulating factor (IL-12) mRNA and protein secretion was strongly induced by lipopolysaccharide but not by P2 protein. Supernatants harvested from P2-stimulated monocytes contained signicant amounts of TNF, IL-118, and IL-8, whereas those from macrophages contained only TNF and IL-8. The effect of the P2 protein on TNF and IL-8 mRNA accumulation and secretion was not affected by polymyxin B, which, on the other hand, almost completely abolished the effect of lipopolysaccharide. Finally, P2 protein did not directly trigger hydrogen peroxide release but, through the induced release of TNF, potentiated monocyte respiratory burst capability. Since P2 protein is the antigen responsible for the induction of experimental allergic neuritis, these findings identify a potential mechanism involved in the infammatory reaction and myelin damage during experimental allergic neuritis.P2 is a 14-kDa basic protein found in myelin and in the cytosol of Schwann cells and oligodendrocytes. P2 protein is the crucial antigen responsible for the immune events associated with experimental allergic neuritis (EAN) (1), an autoimmune demyelinating disease of the peripheral nervous system (PNS) proposed as an animal model of the acute human Guillain-Barrd syndrome (2).Mononuclear phagocytes are the predominant inflammatory cell type in the PNS during EAN and their role in the effector phase and amplification of the disease has been well established (3, 4). Even though previous studies showed that during EAN macrophages phagocytize the myelin sheath (5) and inflict myelin damage by releasing inflammatory mediators such as reactive oxygen intermediates (ROIs), arachidonic acid metabolites, and hydrolases (6, 7), the mechanisms by which these processes occur are unknown.The present study was designed to examine whether mononuclear phagocytes generate potentially injurious mediators upon interaction with purified P2 protein. We observed that P2 protein induced the production of tumor necrosis factor (TNF), interleukin 13 (IL-1p), and interleukin 8 (IL-8), did not stimulate ROI release from phagocytes, and activated monocyte respiratory burst capability. Our findings show that specific myelin components can regulate inflammatory and immunological responses and add further insights on the role of phagocytic cells in the effector mechanisms during EAN.

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supporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein.

Baron

Constantin

D’Andrea

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…All the inhibitors used were not toxic for the cells as shown by the lack of effect on the stimulation of H 2 O 2 production by PMA (data not shown). (50) and other (51,52) laboratories have shown that the stimulus-induced activation of the NADPH oxidase of macrophages can be potentiated by treatment with cytokines, mostly IFN-␥ or TNF-␣, and that this potentiation is due to the increased expression of oxidase components (50 -54). It has been also shown that the maturation of monocytes to macrophages resulted in a progressive loss of the capability to produce ROI (51, 53) due to decreased expression of NADPH oxidase components (50,51,54).…”

Section: A␤ Peptides Stimulate the Production Of Roi-the Results Ofmentioning

confidence: 99%

β-Amyloid Activates the O⨪2 Forming NADPH Oxidase in Microglia, Monocytes, and Neutrophils

Bianca¹,

Dusi²,

Bianchini³

et al. 1999

Journal of Biological Chemistry

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286

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The deposition of ␤-amyloid in the brain is the key pathogenetic event in Alzheimer's disease. Among the various mechanisms proposed to explain the neurotoxicity of ␤-amyloid deposits, a new one, recently identified in our and other laboratories, suggests that ␤-amyloid is indirectly neurotoxic by activating microglia to produce toxic inflammatory mediators such as cytokines, nitric oxide, and oxygen free radicals. Three findings presented here support this mechanism, showing that ␤-amyloid peptides (25-35), (1-39), and (1-42) activated the classical NADPH oxidase in rat primary culture of microglial cells and human phagocytes: 1) The exposure of the cells to ␤-amyloid peptides stimulates the production of reactive oxygen intermediates; 2) the stimulation is associated with the assembly of the cytosolic components of NADPH oxidase on the plasma membrane, the process that corresponds to the activation of the enzyme; 3) neutrophils and monocytes of chronic granulomatous disease patients do not respond to ␤-amyloid peptides with the stimulation of reactive oxygen intermediate production. Data are also presented that the activation of NADPH oxidase requires that ␤-amyloid peptides be in fibrillary state, is inhibited by inhibitors of tyrosine kinases or phosphatidylinositol 3-kinase and by dibutyryl cyclic AMP, and is potentiated by interferon-␥ or tumor necrosis factor-␣.The most common form of senile dementia, Alzheimer's disease (AD), 1 is characterized by a progressive loss of neurons from particular regions of the brain, by the formation of neurofibrillary tangles in neurons, and by numerous senile plaques in affected brain regions. The major component of the senile plaques is the ␤-amyloid protein (A␤), a 39 -43-amino acid peptide, derived from a larger transmembrane glycoprotein called ␤-amyloid precursor protein (1). The A␤ of the senile plaques consists of fibrils that are 4 -10 nm in diameter and exhibit green birefringence under polarized illumination when stained with Congo Red. According to spectroscopic and x-ray diffraction studies, the amyloid fibril assembly is correlated with the adoption of a ␤-sheet structure (2, 3).According to the "␤-amyloid cascade'' hypothesis, the excessive deposition of A␤ is the key pathogenetic event in AD (4 -8) and would be responsible for neurodegenerative changes of neurons. In the plaques the central deposit of extracellular amyloid fibrils (the core) is surrounded by dystrophic neurites (dendrites and axon terminals) and by activated microglia and reactive astrocytes (9, 10). Furthermore, it has been demonstrated that A␤ is neurotoxic in vitro (7,11,12) and that this toxicity correlates with ␤-sheet structure and fibrillary state (Ref. 13; Ref. 7 and references therein). Data have been also provided showing that it is the amphiphilic nature of the peptides rather than their ␤ structure per se that causes toxicity (14).Studies of A␤ cytotoxicity have resulted in some broad concepts of mechanism that are not mutually exclusive (7,15). One proposes that A␤ can directl...

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“…This has been attributed to down-modulation of the mRNA for constituents of the NADPH oxidase, specifically the membrane-associated gp91 and the cytosolic p47 components (40,41). The culture of monocytes with IFN-y during maturation increases the expression of gp91 and p47, paralleling the increase in respiratory burst activity in these cells (40,41). In addition, IFN-y alters the signaling pathways involved in regulating respiratory burst activity, specifically modulation of intracellular Ca2+ levels.…”

Section: Resultsmentioning

confidence: 99%

Interferon-γ Corrects the Respiratory Burst Defect In Vitro in Monocyte-Derived Macrophages from Glycogen Storage Disease Type 1b Patients

et al. 1993

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Studies on the gene expression of several NADPH oxidase components

Cited by 17 publications

References 3 publications

Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein.

Production of tumor necrosis factor and other proinflammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein.

β-Amyloid Activates the O⨪2 Forming NADPH Oxidase in Microglia, Monocytes, and Neutrophils

Interferon-γ Corrects the Respiratory Burst Defect In Vitro in Monocyte-Derived Macrophages from Glycogen Storage Disease Type 1b Patients

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