Macrophage β-arrestin-1 deteriorates DSS-induced colitis through interaction with NF-κB signaling
Copyright © 2024 Elsevier B.V. All rights reserved..
β-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage β-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid β-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage β-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-α as an inflammatory stressor in vitro. The expression level of β-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-κB activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-κB activation. Our results exposed that the level of β-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-α challenge. Moreover, conditionally knocking out the expression of myeloid β-arrestin-1 alleviated disease severity, while knocking out the expression of β-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-κB was identified as a central regulatory element of β-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-κB activation lowered the level of β-arrestin-1 under TNF-α challenge. β-arrestin-1 led to the activation of the NF-κB signaling pathway by enhancing binding to IκBα and IKK under the TNF-α challenge. Taken together, our findings demonstrated macrophage β-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-κB signaling, thus highlighting a novel target for the treatment of UC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111676 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ke, Ping [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111676 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368575268 |
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| 520 | |a β-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage β-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid β-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage β-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-α as an inflammatory stressor in vitro. The expression level of β-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-κB activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-κB activation. Our results exposed that the level of β-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-α challenge. Moreover, conditionally knocking out the expression of myeloid β-arrestin-1 alleviated disease severity, while knocking out the expression of β-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-κB was identified as a central regulatory element of β-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-κB activation lowered the level of β-arrestin-1 under TNF-α challenge. β-arrestin-1 led to the activation of the NF-κB signaling pathway by enhancing binding to IκBα and IKK under the TNF-α challenge. Taken together, our findings demonstrated macrophage β-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-κB signaling, thus highlighting a novel target for the treatment of UC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a Ulcerative colitis | |
| 650 | 4 | |a β–arrestin–1 | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a 3-(4-methylphenylsulfonyl)-2-propenenitrile |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a beta-Arrestin 1 |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
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| 700 | 1 | |a Zhu, Dan-Ni |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Meng-Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Qing-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiong-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chong |e verfasserin |4 aut | |
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