MicroRNA-302b negatively regulates IL-1ß production in response to MSU crystals by targeting IRAK4 and EphA2.
Arthritis Res Ther
; 20(1): 34, 2018 02 26.
Article
em En
| MEDLINE
| ID: mdl-29482609
ABSTRACT
BACKGROUND:
Interleukin-1ß (IL-1ß) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1ß is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism.METHODS:
The expression pattern and the immune-regulatory role of miR-302b were evaluated both in vitro and in vivo. The functional targets of miR-302b were predicted by bioinformatics, and then validated by genetic approaches. In addition, the clinical feature of miR-302b was analyzed using serum samples of patients with gouty arthritis.RESULTS:
The extremely high expression of miR-302b was observed in both macrophages and mouse air membranes treated with MSU. Intriguingly, overexpression of miR-302b regulated NF-κB and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1ß. By genetic analysis, miR-302b exhibited inhibitory function on IRAK4 and EphA2 by binding to their 3'-UTR regions. Corporately silencing IRAK4 and EphA2 largely impaired MSU-induced IL-1ß protein production. Moreover, it was also found that miR-302b and EphA2 suppressed the migration of macrophages. Finally, it was observed that high expression of miR-302b was a general feature in patients with gouty arthritis.CONCLUSIONS:
These results suggest that miR-302b can regulate IL-1ß production in MSU-induced inflammation by targeting NF-κB and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Úrico
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Receptor EphA2
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MicroRNAs
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Quinases Associadas a Receptores de Interleucina-1
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Interleucina-1beta
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article