miR-23b Attenuates LPS-Induced Inflammatory Responses in Acute Lung Injury via Inhibition of HDAC2.
Biochem Genet
; 59(2): 604-616, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33415668
ABSTRACT
Inflammatory responses play significant role in infectious etiology-induced acute lung injury (ALI). Histone deacetylase 2 is found to be essential and stimulated in lipopolysaccharide (LPS)-induced ALI by regulating proinflammatory cytokines. miR-23b has been demonstrated to be downregulated in LPS-induced inflammatory injury. In this study, we aimed to explore the interaction between miR-23b and HDAC2 and their function in LPS-induced ALI. LPS treatment was induced on murine alveolar macrophage cell line MH-S. Level of miR-23b and HDAC2 were determined by real-time PCR or Western blot. Proinflammatory cytokines expression and secretion were detected by real-time PCR and ELISA assay. The levels of miR-23b and HDAC2 were manipulated by transient transfection of miRNA mimics, shRNA or overexpression vector. The interaction between miR-23b and HDAC2 were tested by Luciferase reporter assay. LPS treatment inhibited miR-23b expression, while increased HDAC2 level in MH-S cells. Proinflammatory cytokines were stimulated by LPS treatment. Knockdown of HDAC2 or overexpression of miR-23b significantly repressed the expression of proinflammatory cytokines induced by LPS. miR-23b could suppress HDAC2 expression by directly targeting to its mRNA. LPS treatment stimulated the inflammatory responses in macrophages through inhibition of miR-23b, enhanced HDAC2 expression and inducing the expression of its downstream targets TNF-α, IL-6, and IL-1ß. Overexpression of miR-23b was sufficient to suppress inflammatory responses by targeting HDAC2, making it a promising therapeutic target to ALI treatment.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
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MicroRNAs
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Lesão Pulmonar Aguda
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Histona Desacetilase 2
Limite:
Animals
Idioma:
En
Revista:
Biochem Genet
Ano de publicação:
2021
Tipo de documento:
Article