P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages
© 2023. The Author(s)..
BACKGROUND: The purinergic receptor P2X7 plays a crucial role in infection, inflammation, and cell death. It is thought that P2X7 receptor stimulation triggers processing and release of the pro-inflammatory cytokine interleukin (IL)-1β by activation of the NLRP3 inflammasome; however, the underlying mechanisms remain poorly understood.
METHODS: Modulation of IL-1β secretion was studied in THP-1 macrophages. Adenosine 5'-triphosphate (ATP), BzATP, nigericin and pharmacological inhibitors of P2X receptors, inflammatory caspases and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome were used to characterize signaling.
RESULTS: In primed macrophages, IL-1β release was increased after P2X7 receptor activation by ATP and 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP). Pharmacological inhibition or genetic knockout of NLRP3 does not completely inhibit IL-1β release in TLR2/1-primed macrophages. Increase in extracellular K+ as well as inhibition of caspase-1 or serine proteases maintained IL-1β release in macrophages stimulated with P2X7 receptor agonists at 50%.
CONCLUSIONS: Our findings suggest a previously unrecognized mechanism of P2X7 receptor mediated IL-1β release and highlight the existence of an NLRP3-independent pathway in human macrophages. Video Abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Cell communication and signaling : CCS - 21(2023), 1 vom: 23. Nov., Seite 335 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bockstiegel, Judith [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.11.2023 Date Revised 25.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12964-023-01356-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364881194 |
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| 100 | 1 | |a Bockstiegel, Judith |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages |
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| 500 | |a Date Revised 25.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: The purinergic receptor P2X7 plays a crucial role in infection, inflammation, and cell death. It is thought that P2X7 receptor stimulation triggers processing and release of the pro-inflammatory cytokine interleukin (IL)-1β by activation of the NLRP3 inflammasome; however, the underlying mechanisms remain poorly understood | ||
| 520 | |a METHODS: Modulation of IL-1β secretion was studied in THP-1 macrophages. Adenosine 5'-triphosphate (ATP), BzATP, nigericin and pharmacological inhibitors of P2X receptors, inflammatory caspases and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome were used to characterize signaling | ||
| 520 | |a RESULTS: In primed macrophages, IL-1β release was increased after P2X7 receptor activation by ATP and 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP). Pharmacological inhibition or genetic knockout of NLRP3 does not completely inhibit IL-1β release in TLR2/1-primed macrophages. Increase in extracellular K+ as well as inhibition of caspase-1 or serine proteases maintained IL-1β release in macrophages stimulated with P2X7 receptor agonists at 50% | ||
| 520 | |a CONCLUSIONS: Our findings suggest a previously unrecognized mechanism of P2X7 receptor mediated IL-1β release and highlight the existence of an NLRP3-independent pathway in human macrophages. Video Abstract | ||
| 650 | 4 | |a Video-Audio Media | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Human macrophages | |
| 650 | 4 | |a IL-1beta | |
| 650 | 4 | |a NLRP3 inflammasome | |
| 650 | 4 | |a P2X7 receptor | |
| 650 | 4 | |a Toll-like receptors | |
| 650 | 7 | |a Adenosine Triphosphate |2 NLM | |
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| 650 | 7 | |a Interleukin-1beta |2 NLM | |
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| 650 | 7 | |a Receptors, Purinergic P2X7 |2 NLM | |
| 650 | 7 | |a NLRP3 protein, human |2 NLM | |
| 650 | 7 | |a P2RX7 protein, human |2 NLM | |
| 650 | 7 | |a IL1B protein, human |2 NLM | |
| 700 | 1 | |a Engelhardt, Jonas |e verfasserin |4 aut | |
| 700 | 1 | |a Weindl, Günther |e verfasserin |4 aut | |
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