Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Inflammasome activation culminates in activation of caspase-1, which leads to the maturation and subsequent release of cytokines of the interleukin 1 (IL-1) family and results in a particular form of cell death known as pyroptosis. In addition, in the murine system, a so-called non-canonical inflammasome involving caspase-11 has been described that directly responds to cytosolic LPS. Here, we show that the human monocytic cell line THP1 activates the inflammasome in response to cytosolic LPS in a TLR4-independent fashion. This response is mediated by caspase-4 and accompanied by caspase-1 activation, pyroptosis, and IL-1β maturation. In addition to caspase-4, efficient IL-1β conversion upon intracellular LPS delivery relies on potassium efflux, NLRP3, ASC, and caspase-1, indicating that although caspase-4 activation alone is sufficient to induce pyroptosis, this process depends on the NLRP3 inflammasome activation to drive IL-1β maturation. Altogether, this study provides evidence for the presence of a non-canonical inflammasome in humans and its dependence on caspase-4.
| Errataetall: |
ErratumIn: Eur J Immunol. 2021 Jun;51(6):1546. - PMID 34096070 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
European journal of immunology - 45(2015), 10 vom: 15. Okt., Seite 2911-7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schmid-Burgk, Jonathan L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.01.2016 Date Revised 07.06.2021 published: Print-Electronic ErratumIn: Eur J Immunol. 2021 Jun;51(6):1546. - PMID 34096070 Citation Status MEDLINE |
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| doi: |
10.1002/eji.201545523 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM250877104 |
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| 245 | 1 | 0 | |a Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells |
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| 500 | |a ErratumIn: Eur J Immunol. 2021 Jun;51(6):1546. - PMID 34096070 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Inflammasome activation culminates in activation of caspase-1, which leads to the maturation and subsequent release of cytokines of the interleukin 1 (IL-1) family and results in a particular form of cell death known as pyroptosis. In addition, in the murine system, a so-called non-canonical inflammasome involving caspase-11 has been described that directly responds to cytosolic LPS. Here, we show that the human monocytic cell line THP1 activates the inflammasome in response to cytosolic LPS in a TLR4-independent fashion. This response is mediated by caspase-4 and accompanied by caspase-1 activation, pyroptosis, and IL-1β maturation. In addition to caspase-4, efficient IL-1β conversion upon intracellular LPS delivery relies on potassium efflux, NLRP3, ASC, and caspase-1, indicating that although caspase-4 activation alone is sufficient to induce pyroptosis, this process depends on the NLRP3 inflammasome activation to drive IL-1β maturation. Altogether, this study provides evidence for the presence of a non-canonical inflammasome in humans and its dependence on caspase-4 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Caspase-4 | |
| 650 | 4 | |a Myeloid cells | |
| 650 | 4 | |a NLRP3 | |
| 650 | 4 | |a Non-canonical inflammasome | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a IL1B protein, human |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a NLRP3 protein, human |2 NLM | |
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| 650 | 7 | |a Caspases, Initiator |2 NLM | |
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| 650 | 7 | |a Caspase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.36 |2 NLM | |
| 700 | 1 | |a Gaidt, Moritz M |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Ebert, Thomas S |e verfasserin |4 aut | |
| 700 | 1 | |a Bartok, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Hornung, Veit |e verfasserin |4 aut | |
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