Reference : Regulated in development and DNA damage responses 1 (REDD1) links stress with IL-1β-m...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/32916
Regulated in development and DNA damage responses 1 (REDD1) links stress with IL-1β-mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps
English
Skendros, P. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece, First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
Chrysanthopoulou, A. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Rousset, F. [Université Pierre et Marie Curie, UF d'Histocompatibilité et Immunogénétique, Département d'Immunologie, Groupe Hospitalier Pitié Salpêtrière-Charles Foix, Paris, France]
Kambas, K. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Arampatzioglou, A. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Mitsios, A. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Bocly, V. [Université Pierre et Marie Curie, UF d'Histocompatibilité et Immunogénétique, Département d'Immunologie, Groupe Hospitalier Pitié Salpêtrière-Charles Foix, Paris, France]
Konstantinidis, T. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Pellet, P. [Université Pierre et Marie Curie, UF d'Histocompatibilité et Immunogénétique, Département d'Immunologie, Groupe Hospitalier Pitié Salpêtrière-Charles Foix, Paris, France]
Angelidou, I. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Apostolidou, E. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece, First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
Ritis, D. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Tsironidou, V. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Galtsidis, Sotirios mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Papagoras, C. [First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
Stakos, D. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece]
Kouklakis, G. [First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
Dalla, V. [First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
Koffa, Maria mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Mitroulis, I. [Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine Technische Universität Dresden, Dresden, Germany]
Theodorou, I. [Université Pierre et Marie Curie, UF d'Histocompatibilité et Immunogénétique, Département d'Immunologie, Groupe Hospitalier Pitié Salpêtrière-Charles Foix, Paris, France]
Ritis, K. [Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece, First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece]
23-Mar-2017
Journal of Allergy and Clinical Immunology
Mosby Inc.
Yes (verified by ORBilu)
00916749
[en] Autophagy ; Familiar Mediterranean fever ; IL-1β ; Inflammation ; Neutrophil extracellular traps ; Regulated in development and DNA damage responses 1 ; Stress
[en] Background: Familial Mediterranean fever (FMF) is an IL-1β-dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress. Objective: We investigated the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1β-bearing neutrophil extracellular traps (NETs) in patients with FMF. Methods: RNA sequencing was performed in peripheral neutrophils from 3 patients with FMF isolated both during attacks and remission, 8 patients in remission, and 8 healthy subjects. NET formation and proteins were analyzed by using confocal immunofluorescence microscopy, immunoblotting, myeloperoxidase-DNA complex ELISA, and flow cytometry. Samples from patients with Still's disease and bacterial infections were used also. Results: The stress-related protein regulated in development and DNA damage responses 1 (REDD1) is significantly overexpressed during FMF attacks. Neutrophils from patients with FMF during remission are resistant to autophagy-mediated NET release, which can be overcome through REDD1 induction. Stress-related mediators (eg, epinephrine) decrease this threshold, leading to autophagy-driven NET release, whereas the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1β and its release through NETs. REDD1 in autolysosomes colocalizes with pyrin and nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3. Mutated pyrin prohibits this colocalization, leading to higher IL-1β levels on NETs. Conclusions: This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1β, and might constitute an important piece in the IL-1β-mediated inflammation puzzle. © 2017 American Academy of Allergy, Asthma & Immunology.
http://hdl.handle.net/10993/32916
10.1016/j.jaci.2017.02.021

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