IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease. Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated the effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes. IAPs inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory interleukin (IL)-1β, IL-6. Likewise, LPS (but not muramyl dipeptide or Escherichia coli) induced TNF-α was inhibited in CD and control PBMCs. The SM effect was partially reversed by inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The effect was mainly cell death independent. Thus, IAP inhibition by SMs leads to reduced production of proinflammatory cytokines and may be considered in the efforts to develop new therapeutic strategies to control CD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:215 |
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| Enthalten in: |
Clinical and experimental immunology - 215(2024), 3 vom: 19. Feb., Seite 291-301 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Seidelin, Jakob Benedict [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.02.2024 Date Revised 09.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cei/uxad092 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease. Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated the effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes. IAPs inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory interleukin (IL)-1β, IL-6. Likewise, LPS (but not muramyl dipeptide or Escherichia coli) induced TNF-α was inhibited in CD and control PBMCs. The SM effect was partially reversed by inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The effect was mainly cell death independent. Thus, IAP inhibition by SMs leads to reduced production of proinflammatory cytokines and may be considered in the efforts to develop new therapeutic strategies to control CD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Crohn’s disease | |
| 650 | 4 | |a human monocyte activation | |
| 650 | 4 | |a inhibitor of apoptosis proteins | |
| 650 | 4 | |a lipopolysaccharide | |
| 650 | 4 | |a receptor-interacting serine/threonine-protein kinase 1 | |
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| 700 | 1 | |a Jensen, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Morten |e verfasserin |4 aut | |
| 700 | 1 | |a de Carvalho Bronze, Mariana Rodrigues |e verfasserin |4 aut | |
| 700 | 1 | |a Cuchet-Lourenҫo, Delphine |e verfasserin |4 aut | |
| 700 | 1 | |a Nejentsev, Sergey |e verfasserin |4 aut | |
| 700 | 1 | |a LaCasse, Eric Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Ole Haagen |e verfasserin |4 aut | |
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