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- W2598647084 abstract "BackgroundFamilial 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.ObjectiveWe 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.MethodsRNA 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.ResultsThe 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.ConclusionsThis 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. 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. 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. 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. 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. 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." @default.
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- W2598647084 date "2017-11-01" @default.
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- W2598647084 title "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" @default.
- W2598647084 cites W1819753035 @default.
- W2598647084 cites W1948540998 @default.
- W2598647084 cites W1966104640 @default.
- W2598647084 cites W1971141285 @default.
- W2598647084 cites W1974781808 @default.
- W2598647084 cites W1981345340 @default.
- W2598647084 cites W1994705699 @default.
- W2598647084 cites W1995383659 @default.
- W2598647084 cites W2001219687 @default.
- W2598647084 cites W2015902169 @default.
- W2598647084 cites W2019427203 @default.
- W2598647084 cites W2020908160 @default.
- W2598647084 cites W2021880506 @default.
- W2598647084 cites W2025449580 @default.
- W2598647084 cites W2032687345 @default.
- W2598647084 cites W2033698154 @default.
- W2598647084 cites W2036092039 @default.
- W2598647084 cites W2038952117 @default.
- W2598647084 cites W2042767581 @default.
- W2598647084 cites W2047525024 @default.
- W2598647084 cites W2055313736 @default.
- W2598647084 cites W2070794927 @default.
- W2598647084 cites W2076507733 @default.
- W2598647084 cites W2077001140 @default.
- W2598647084 cites W2090539879 @default.
- W2598647084 cites W2091512988 @default.
- W2598647084 cites W2092429129 @default.
- W2598647084 cites W2093154865 @default.
- W2598647084 cites W2095917499 @default.
- W2598647084 cites W2098610477 @default.
- W2598647084 cites W2101271919 @default.
- W2598647084 cites W2103441770 @default.
- W2598647084 cites W2108234281 @default.
- W2598647084 cites W2111589020 @default.
- W2598647084 cites W2114104545 @default.
- W2598647084 cites W2115820946 @default.
- W2598647084 cites W2120372473 @default.
- W2598647084 cites W2124335748 @default.
- W2598647084 cites W2130735667 @default.
- W2598647084 cites W2134526812 @default.
- W2598647084 cites W2134735862 @default.
- W2598647084 cites W2140729960 @default.
- W2598647084 cites W2141522272 @default.
- W2598647084 cites W2148197020 @default.
- W2598647084 cites W2158721132 @default.
- W2598647084 cites W2162647701 @default.
- W2598647084 cites W2170423778 @default.
- W2598647084 cites W2170538350 @default.
- W2598647084 cites W2170708401 @default.
- W2598647084 cites W2262791344 @default.
- W2598647084 cites W2344202261 @default.
- W2598647084 cites W2396063348 @default.
- W2598647084 cites W2418840180 @default.
- W2598647084 cites W2464031336 @default.
- W2598647084 doi "https://doi.org/10.1016/j.jaci.2017.02.021" @default.
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