Expression of p47-phox and p67-phox proteins in murine bone marrow–derived macrophages: Enhancement by lipopolysaccharide and tumor necrosis factor α but not colony stimulating factor 1

Green, Simon P.; Hamilton, John A.; Uhlinger, David J.; Phillips, Wayne A.

doi:10.1002/jlb.55.4.530

Cited by 27 publications

(16 citation statements)

References 23 publications

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“…The most commonly studied are TNFα, retinoic acid, 1,25 (OH) 2 -vitamin D 3 , LPS and IFNγ. For example, the gene expression of the phagocyte cytosolic protein p47 phox component of NADPH oxidase is up-regulated by TNFα, retinoic acid, 1,25 (OH) 2 -vitamin D 3 , and LPS, but down-regulated by IFNγ [42]–[44]. In contrast, IFNγ induces the expression of FcR and certain chemokine receptors (CCR1, CCR3 and CCR5) in U937 cells [45], [46].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators

Miettinen

2011

PLoS ONE

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The gene encoding the human formyl peptide receptor 1 (FPR1) is heterogeneous, containing numerous single nucleotide polymorphisms (SNPs). Here, we examine the effect of these SNPs on gene transcription and protein translation. We also identify gene promoter sequences and putative FPR1 transcription factors. To test the effect of codon bias and codon pair bias on FPR1 expression, four FPR1 genetic variants were expressed in human myeloid U937 cells fused to a reporter gene encoding firefly luciferase. No significant differences in luciferase activity were detected, suggesting that the translational regulation and protein stability of FPR1 are modulated by factors other than the SNP codon bias and the variant amino acid properties. Deletion and mutagenesis analysis of the FPR1 promoter showed that a CCAAT box is not required for gene transcription. A −88/41 promoter construct resulted in the strongest transcriptional activity, whereas a −72/41 construct showed large reduction in activity. The region between −88 and −72 contains a consensus binding site for the transcription factor PU.1. Mutagenesis of this site caused significant reduction in reporter gene expression. The PU.1 binding was confirmed in vivo by chromatin immunoprecipitation, and the binding to nucleotides −84 to −76 (TTCCTATTT) was confirmed in vitro by an electrophoretic mobility shift assay. Thus, similar to many other myeloid genes, FPR1 promoter activity requires PU.1. Two single nucleotide polymorphisms at −56 and −54 did not significantly affect FPR1 gene expression, despite differences in binding of transcription factor IRF1 in vitro. Inflammatory mediators such as interferon-γ, tumor necrosis factor-α, and lipopolysaccharide did not increase FPR1 promoter activity in myeloid cells, whereas differentiation induced by DMSO and retinoic acid enhanced the activity. This implies that the expression of FPR1 in myeloid cells is developmentally regulated, and that the differentiated cells are equipped for immediate response to microbial infections.

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Section: Discussionmentioning

confidence: 99%

Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators

Miettinen

2011

PLoS ONE

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“…9,10,30 Among these, p47phox, which is known as neutrophil cytosol factor-1, is a subunit mainly expressed in neutrophils and macrophages. 9,10,31,32 Deletion of p47phox attenuated abdominal aortic aneurysms in mice. 28 The p47phox subunit of NADPH oxidase was mainly expressed in macrophages infiltrating CA walls and was upregulated during CA formation and progression (Figures 2-4).…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species modulate growth of cerebral aneurysms: a study using the free radical scavenger edaravone and p47phox−/− mice

Aoki

Nakagawa

Kataoka

et al. 2009

Laboratory Investigation

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Cerebral aneurysm (CA) is a relatively common disease and can cause a catastrophic subarachnoid hemorrhage with a high mortality and morbidity rate. Despite its clinical and social importance, the detailed mechanism of CA formation remains to be elucidated, resulting in the absence of effective medical treatment against CAs. Recent studies revealed that chronic inflammation in arterial walls by hemodynamic force is implicated in CA formation. Reactive oxygen species (ROS) are a major mediator of inflammation and actively participate in the pathogenesis of various vascular diseases. In the present study, we first assessed the expression of ROS-producing and -eliminating genes in CA walls by immunohistochemistry and RT-PCR analysis. The ROS-producing gene, p47phox, was upregulated in infiltrating macrophages and medial smooth muscle cells in arterial walls. Upregulated ROS-producing genes and suppressed ROS-eliminating genes suggested that ROS overproduction occurred in aneurysmal walls. In situ superoxide imaging by dihydroethidium, which showed ROS overproduction in aneurysmal walls, confirmed this hypothesis. Edaravone, a powerful free radical scavenger, effectively inhibited CA formation by suppressing inflammation-related gene expression in aneurysmal walls. Furthermore, CA formation was markedly inhibited by p47phox deletion in mice and was accompanied by decreased inflammation in aneurysmal walls. These data suggested the active participation of ROS and p47phox in CA formation and the therapeutic potential of an ROS-eliminating agent against CA formation.

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“…The cytosol and membrane fractions were stored at Ϫ80°C until SDS-PAGE analysis. For analysis of translocation of cytosolic proteins, the membrane fractions were separated by SDS-PAGE, and the proteins were transferred to nitrocellulose and immunoblotted sequentially with polyclonal anti-p47 phox , polyclonal anti-p67 phox (27) (both kindly provided by David Lambeth, Emory University), monoclonal anti-Rac1 (Upstate Biotechnology, Inc.), polyclonal anti-Rac2 (7) (kindly provided by Gary Bokoch, The Scripps Research Institute), and polyclonal anti-Rap1a (28) (kindly provided by Mark Quinn, Montana State University) and developed with the ECL detection system (Amersham Pharmacia Biotech) as described previously (18). Integrated densitometry was employed to measure the relative intensity of the protein signal using an Eagle Eye II Still Video System and associated software (Stratagene).…”

Section: Methodsmentioning

confidence: 99%

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

Biberstine-Kinkade¹,

Yu²,

Dinauer

1999

Journal of Biological Chemistry

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Expression of p47-phox and p67-phox proteins in murine bone marrow–derived macrophages: Enhancement by lipopolysaccharide and tumor necrosis factor α but not colony stimulating factor 1

Cited by 27 publications

References 23 publications

Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators

Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators

Reactive oxygen species modulate growth of cerebral aneurysms: a study using the free radical scavenger edaravone and p47phox−/− mice

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

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