Kawasaki disease : ubiquitin-specific protease 5 promotes endothelial inflammation via TNFα-mediated signaling
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc..
BACKGROUND: This study aimed to explore the functions of ubiquitin-specific protease 5 (USP5) in the endothelial inflammation of Kawasaki disease (KD).
METHODS: USP5 expression levels in HCAECs were examined after stimulation with TNFα or KD sera. The inflammatory cytokine expression level and nuclear factor κB (NF-κB) signaling activation proteins were also investigated in HCAECs by using USP5 overexpression/knockdown lentivirus as well as its small molecule inhibitor vialinin A.
RESULTS: USP5 expression level is upregulated in HCAECs after stimulation with KD sera. Similarly, the USP5 expression level is also increased in a time- and dose-dependent manner upon TNFα stimulation in HCAECs. Moreover, USP5 sustains proinflammatory cytokine production and NF-κB signaling activation, whereas USP5 knockdown causes the proinflammatory cytokine levels to decrease and suppress NF-κB signaling activation. Notably, the USP5 inhibitor vialinin A can suppress the expression of inflammatory genes induced by TNFα and IL-1β in HCAECs.
CONCLUSIONS: Our study identified USP5 as a positive regulator of TNFα production and its downstream signaling activation during the inflammatory responses in HCAECs, and demonstrated that its inhibitor vialinin A might serve as a candidate drug for KD therapy to prevent the excessive production of proinflammatory cytokines.
IMPACT: USP5 is upregulated in human coronary artery endothelial cells (HCAECs) whether incubated with acute KD sera or TNFα in vitro. USP5 promotes proinflammatory cytokine expression by sustaining NF-κB signaling activation in HCAECs. The USP5 inhibitor vialinin A can suppress the expression levels of proinflammatory cytokines in HCAEC, thus providing a novel mechanism and intervention strategy in KD therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:93 |
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| Enthalten in: |
Pediatric research - 93(2023), 7 vom: 19. Juni, Seite 1883-1890 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Chengcheng [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 11.07.2023 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41390-022-02341-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348431422 |
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| 100 | 1 | |a Huang, Chengcheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Kawasaki disease |b ubiquitin-specific protease 5 promotes endothelial inflammation via TNFα-mediated signaling |
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| 500 | |a Date Revised 22.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc. | ||
| 520 | |a BACKGROUND: This study aimed to explore the functions of ubiquitin-specific protease 5 (USP5) in the endothelial inflammation of Kawasaki disease (KD) | ||
| 520 | |a METHODS: USP5 expression levels in HCAECs were examined after stimulation with TNFα or KD sera. The inflammatory cytokine expression level and nuclear factor κB (NF-κB) signaling activation proteins were also investigated in HCAECs by using USP5 overexpression/knockdown lentivirus as well as its small molecule inhibitor vialinin A | ||
| 520 | |a RESULTS: USP5 expression level is upregulated in HCAECs after stimulation with KD sera. Similarly, the USP5 expression level is also increased in a time- and dose-dependent manner upon TNFα stimulation in HCAECs. Moreover, USP5 sustains proinflammatory cytokine production and NF-κB signaling activation, whereas USP5 knockdown causes the proinflammatory cytokine levels to decrease and suppress NF-κB signaling activation. Notably, the USP5 inhibitor vialinin A can suppress the expression of inflammatory genes induced by TNFα and IL-1β in HCAECs | ||
| 520 | |a CONCLUSIONS: Our study identified USP5 as a positive regulator of TNFα production and its downstream signaling activation during the inflammatory responses in HCAECs, and demonstrated that its inhibitor vialinin A might serve as a candidate drug for KD therapy to prevent the excessive production of proinflammatory cytokines | ||
| 520 | |a IMPACT: USP5 is upregulated in human coronary artery endothelial cells (HCAECs) whether incubated with acute KD sera or TNFα in vitro. USP5 promotes proinflammatory cytokine expression by sustaining NF-κB signaling activation in HCAECs. The USP5 inhibitor vialinin A can suppress the expression levels of proinflammatory cytokines in HCAEC, thus providing a novel mechanism and intervention strategy in KD therapy | ||
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| 700 | 1 | |a Huang, Hongbiao |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yueyue |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Pu, Xiangqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Guanghui |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Haitao |e verfasserin |4 aut | |
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