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-1β. 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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Funding
This work was supported by The Hunan Provincial Natural Science Fund of China (No. 2015JJ2131), The Scientific Research Projects of Hunan Provincial Educational Department (No. 13C890), The Medical Research Plan Projects Foundation of Hunan Provincial Health Department (No. B2014-070), The Scientific Research Fund of Xiangnan University (No. 2011YY47), The Chenzhou Municipal Key Research and Development and Technology Innovation Guiding Funds (No. Zdyf201811), The Research Learning and Innovative Experiment Plan for College Students of Xiangnan University in 2013 (No. 87) and The Research Learning and Innovative Experiment Plan for College Students of Xiangnan University in 2018 (No. 56).
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Luo, ZF., Jiang, XH., Liu, H. et al. miR-23b Attenuates LPS-Induced Inflammatory Responses in Acute Lung Injury via Inhibition of HDAC2. Biochem Genet 59, 604–616 (2021). https://doi.org/10.1007/s10528-020-10018-7
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DOI: https://doi.org/10.1007/s10528-020-10018-7