Antagonizing interleukin-5 receptor ameliorates dextran sulfate sodium-induced experimental colitis in mice through reducing NLRP3 inflammasome activation
Copyright © 2024 Elsevier B.V. All rights reserved..
Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1β and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1β release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:965 |
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| Enthalten in: |
European journal of pharmacology - 965(2024) vom: 15. Feb., Seite 176331 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ou, Yitao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.02.2024 Date Revised 05.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2024.176331 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367106876 |
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| 245 | 1 | 0 | |a Antagonizing interleukin-5 receptor ameliorates dextran sulfate sodium-induced experimental colitis in mice through reducing NLRP3 inflammasome activation |
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| 520 | |a Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1β and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1β release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ASC speck | |
| 650 | 4 | |a Inflammatory bowel disease | |
| 650 | 4 | |a Interleukin-5 receptor | |
| 650 | 4 | |a NLRP3 inflammasome | |
| 650 | 4 | |a YM-90709 | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a Dextran Sulfate |2 NLM | |
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| 650 | 7 | |a Receptors, Interleukin-5 |2 NLM | |
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| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 700 | 1 | |a Yang, Zhongjin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhuorong |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Geng |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Haowei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yanhong |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Wenhui |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ping |e verfasserin |4 aut | |
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