Protective Effect of Inflammasome Activation by Hydrogen Peroxide in a Mouse Model of Septic Shock.
Crit Care Med
; 45(2): e184-e194, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-27749344
ABSTRACT
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 MAINRESULTS:
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-1ß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Inflamassomos
/
Peróxido de Hidrogênio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article