NDLI: ATP modulates acute inflammation in vivo through dual oxidase 1-derived H2O2 production and NF-κB activation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	de Oliveira, Sofia Candel, Sergio Pelegrín, Pablo Calado, Ângelo Mulero, Victoriano López-Muñoz, Azucena
Description	Author Affiliation: de Oliveira S ( Laboratório de Carlota Saldanha, Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal); López-Muñoz A ( Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain); Candel S ( Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain); Pelegrín P ( Instituto Murciano de Investigación Biosanitaria, 30120 Murcia, Spain); Calado Â ( Laboratório de Carlota Saldanha, Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal); Mulero V ( Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain)
Abstract	Dual oxidase 1 (Duox1) is the NADPH oxidase responsible for the H2O2 gradient formed in tissues after injury to trigger the early recruitment of leukocytes. Little is known about the signals that modulate H2O2 release from DUOX1 and whether the H2O2 gradient can orchestrate the inflammatory response in vivo. In this study, we report on a dominant-negative form of zebrafish Duox1 that is able to inhibit endogenous Duox1 activity, H2O2 release and leukocyte recruitment after tissue injury, with none of the side effects associated with morpholino-mediated Duox1 knockdown. Using this specific tool, we found that ATP release following tissue injury activates purinergic P2Y receptors, and modulates Duox1 activity through phospholipase C (PLC) and intracellular calcium signaling in vivo. Furthermore, Duox1-derived H2O2 is able to trigger the NF-κB inflammatory signaling pathway. These data reveal that extracellular ATP acting as an early danger signal is responsible for the activation of Duox1 via a P2YR/PLC/Ca(2+) signaling pathway and the production of H2O2, which, in turn, is able to modulate in vivo not only the early recruitment of leukocytes to the wound but also the inflammatory response through activation of the NF-κB signaling pathway.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenosine Triphosphate Immunology Calcium Signaling Hydrogen Peroxide Nadph Oxidase Nf-kappa B Wounds And Injuries Zebrafish Proteins Acute Disease Animals Inflammation Receptors, Purinergic P2y Zebrafish Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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