Critical care medicine · 2017
Protective Effect of Inflammasome Activation by Hydrogen Peroxide in a Mouse Model of Septic Shock.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Huet Olivier, Pickering Raelene J, Tikellis Chris, Latouche Celine, Long Fenella, Kingwell Bronwyn, Dickinson Bryan, Chang Chris J, Masters Seth, Mackay Fabienne, Cooper Mark E, de Haan Judy B
Аннотация
OBJECTIVES: To study the effect of a lack of antioxidant defenses during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice.
SETTING: Laboratory experiments.
SUBJECTS: C57Bl6 and glutathione peroxidase 1 knockout mice.
INTERVENTION: Murine acute pneumonia model induced by Klebsiella pneumonia.
MEASUREMENTS AND MAIN RESULTS: We show here that despite a lack of one of the major antioxidant defense enzymes, glutathione peroxidase 1 knockout mice are protected during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice. Furthermore, this protective effect was suppressed when antioxidant defenses were restored. Infected glutathione peroxidase 1 mice showed an early and significant, albeit transient, increase in the activity of the NOD-like receptor family, pyrin domain containing 3 inflammasome when compared with wild-type mice. The key role of the NOD-like receptor family, pyrin domain containing 3 inflammasome during acute pneumonia was confirmed in vivo when the protective effect was suppressed by treating glutathione peroxidase 1 mice with an interleukin-1 receptor antagonist. Additionally we report, in vitro, that increased concentrations of active caspase-1 and interleukin-1β are related to an increased concentration of hydrogen peroxide in bacterially infected glutathione peroxidase 1 macrophages and that restoring hydrogen peroxide antioxidant defenses suppressed this effect.
CONCLUSIONS: Our findings demonstrate that, contrary to current thinking, an early intervention targeting NOD-like receptor family, pyrin domain containing 3 inflammasome activity induces a timely and efficient activation of the innate immune response during acute infection. Our findings also demonstrate a role for hydrogen peroxide in the mechanisms tightly regulating NOD-like receptor family, pyrin domain containing 3 activation.
SETTING: Laboratory experiments.
SUBJECTS: C57Bl6 and glutathione peroxidase 1 knockout mice.
INTERVENTION: Murine acute pneumonia model induced by Klebsiella pneumonia.
MEASUREMENTS AND MAIN RESULTS: We show here that despite a lack of one of the major antioxidant defense enzymes, glutathione peroxidase 1 knockout mice are protected during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice. Furthermore, this protective effect was suppressed when antioxidant defenses were restored. Infected glutathione peroxidase 1 mice showed an early and significant, albeit transient, increase in the activity of the NOD-like receptor family, pyrin domain containing 3 inflammasome when compared with wild-type mice. The key role of the NOD-like receptor family, pyrin domain containing 3 inflammasome during acute pneumonia was confirmed in vivo when the protective effect was suppressed by treating glutathione peroxidase 1 mice with an interleukin-1 receptor antagonist. Additionally we report, in vitro, that increased concentrations of active caspase-1 and interleukin-1β are related to an increased concentration of hydrogen peroxide in bacterially infected glutathione peroxidase 1 macrophages and that restoring hydrogen peroxide antioxidant defenses suppressed this effect.
CONCLUSIONS: Our findings demonstrate that, contrary to current thinking, an early intervention targeting NOD-like receptor family, pyrin domain containing 3 inflammasome activity induces a timely and efficient activation of the innate immune response during acute infection. Our findings also demonstrate a role for hydrogen peroxide in the mechanisms tightly regulating NOD-like receptor family, pyrin domain containing 3 activation.
Предметные рубрики MeSH
AnimalsAntioxidantsBlotting, WesternDisease Models, AnimalFemaleGlutathione PeroxidaseHydrogen PeroxideInflammasomesKlebsiella InfectionsKlebsiella pneumoniaeLungMaleMiceMice, Inbred C57BLMice, KnockoutPneumonia, BacterialReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionShock, SepticGlutathione Peroxidase GPX1