Protective Effect of Inflammasome Activation by Hydrogen Peroxide in a Mouse Model of Septic Shock
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Critical care medicine - 45(2017), 2 vom: 01. Feb., Seite e184-e194 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huet, Olivier [VerfasserIn] |
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| Links: |
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| Themen: |
Antioxidants |
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| Anmerkungen: |
Date Completed 24.05.2017 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/CCM.0000000000002070 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM265382831 |
|---|
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| 100 | 1 | |a Huet, Olivier |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Protective Effect of Inflammasome Activation by Hydrogen Peroxide in a Mouse Model of Septic Shock |
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| 500 | |a Date Completed 24.05.2017 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: To study the effect of a lack of antioxidant defenses during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice | ||
| 520 | |a SETTING: Laboratory experiments | ||
| 520 | |a SUBJECTS: C57Bl6 and glutathione peroxidase 1 knockout mice | ||
| 520 | |a INTERVENTION: Murine acute pneumonia model induced by Klebsiella pneumonia | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Hydrogen Peroxide |2 NLM | |
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| 700 | 1 | |a Pickering, Raelene J |e verfasserin |4 aut | |
| 700 | 1 | |a Tikellis, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Latouche, Celine |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Fenella |e verfasserin |4 aut | |
| 700 | 1 | |a Kingwell, Bronwyn |e verfasserin |4 aut | |
| 700 | 1 | |a Dickinson, Bryan |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Chris J |e verfasserin |4 aut | |
| 700 | 1 | |a Masters, Seth |e verfasserin |4 aut | |
| 700 | 1 | |a Mackay, Fabienne |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Mark E |e verfasserin |4 aut | |
| 700 | 1 | |a de Haan, Judy B |e verfasserin |4 aut | |
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