Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-α-induced priming of the NADPH oxidase in human neutrophils
Blood, Volume 116, No. 26, Year 2010
Notification
URL copied to clipboard!
Description
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-a-induced NADPH oxidase hyperactivation. We first showed that Pin1 is expressed in neutrophil cytosol and that its activity is markedly enhanced by TNF-a. Inhibition of Pin1 activity with juglone or with a specific peptide inhibitor abrogated TNF-α-induced priming of neutrophil ROS production induced by N-formylmethionyl-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. © 2010 by The American Society of Hematology.
Authors & Co-Authors
Boussetta, Tarek
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Tunisia, Monastir
Institut Supérieur de Biotechnologie de Monastir
Gougerot-Pocidalo, Marie Anne
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Hayem, Gilles
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Ciappelloni, Silvia
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Raad, Houssam
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Derkawi, Riad Arabi
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Bournier, Odile
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Kroviarski, Yolande
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Zhou, X. Z.
United States, Boston
Harvard Medical School
Malter, James S.
United States, Madison
Waisman Center
Lu, K. P.
United States, Boston
Harvard Medical School
Bartegi, Aghleb B.
France, Paris
Université Paris Cité
Dang, Pham My Chan
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
El-Benna, Jamel
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Statistics
Citations: 93
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.1182/blood-2010-03-273094
ISSN:
00064971
Research Areas
Cancer