| The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils. | |
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MedLine Citation:
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PMID: 20956805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutrophils play a key role in host defense by releasing reactive oxygen species (ROS). However, excessive ROS production by neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can damage bystander tissues, thereby contributing to inflammatory diseases. Tumor necrosis factor-α (TNF-α), a major mediator of inflammation, does not activate NADPH oxidase but induces a state of hyperresponsiveness to subsequent stimuli, an action known as priming. The molecular mechanisms by which TNF-α primes the NADPH oxidase are unknown. Here we show that Pin1, a unique cis-trans prolyl isomerase, is a previously unrecognized regulator of TNF-α-induced NADPH oxidase hyperactivation. We first showed that Pin1 is expressed in neutrophil cytosol and that its activity is markedly enhanced by TNF-α. Inhibition of Pin1 activity with juglone or with a specific peptide inhibitor abrogated TNF-α-induced priming of neutrophil ROS production induced by N-formyl-methionyl-leucyl-phenylalanine peptide (fMLF). TNF-α enhanced fMLF-induced Pin1 and p47phox translocation to the membranes and juglone inhibited this process. Pin1 binds to p47phox via phosphorylated Ser345, thereby inducing conformational changes that facilitate p47phox phosphorylation on other sites by protein kinase C. These findings indicate that Pin1 is critical for TNF-α-induced priming of NADPH oxidase and for excessive ROS production. Pin1 inhibition could potentially represent a novel anti-inflammatory strategy. |
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Authors:
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Tarek Boussetta; Marie-Anne Gougerot-Pocidalo; Gilles Hayem; Silvia Ciappelloni; Houssam Raad; Riad Arabi Derkawi; Odile Bournier; Yolande Kroviarski; Xiao Zhen Zhou; James S Malter; Ping K Lu; Aghleb Bartegi; Pham My-Chan Dang; Jamel El-Benna |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-18 |
Journal Detail:
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Title: Blood Volume: 116 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-24 Completed Date: 2011-02-22 Revised Date: 2012-04-06 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 5795-802 Citation Subset: AIM; IM |
Affiliation:
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Inserm U773, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Membrane / metabolism Cytosol / metabolism Humans N-Formylmethionine Leucyl-Phenylalanine / pharmacology NADPH Oxidase / chemistry, metabolism* Naphthoquinones / pharmacology Neutrophils / drug effects*, enzymology Peptidylprolyl Isomerase / metabolism* Phosphorylation Protein Transport Reactive Oxygen Species / metabolism Tumor Necrosis Factor-alpha / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL088594/HL/NHLBI NIH HHS; P01 HL088594-02/HL/NHLBI NIH HHS; P01 HL088594-03/HL/NHLBI NIH HHS; P01 HL088594-04/HL/NHLBI NIH HHS; P01 HL088594-05/HL/NHLBI NIH HHS; P30 HD03352/HD/NICHD NIH HHS; R01 HL087950/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/NIMA-interacting peptidylprolyl isomerase; 0/Naphthoquinones; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 481-39-0/juglone; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1; EC 5.2.1.8/Peptidylprolyl Isomerase |
| Comments/Corrections | |
Comment In:
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Blood. 2010 Dec 23;116(26):5788-9
[PMID:
21183694
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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