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LncRNA NEAT1 ameliorates LPS?induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome.

ABSTRACT: The mechanisms of inflammation in bone and joint tissue are complex and involve long non?coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were stimulated with various concentrations of lipopolysaccharide (LPS) for different periods of time to construct an optimal inflammatory model and RNA sequencing was then performed on these cells. The levels of nuclear enriched abundant transcript 1 (NEAT1), various inflammatory factors, Nod?like receptor protein 3 (NLRP3) protein and osteogenesis?related proteins, as well as the levels of cell apoptosis? and cell cycle?related markers were measured in MG63 cells stimulated with LPS, transfected with NEAT1 overexpression plasmid and treated with bexarotene by western blot analysis, RT?qPCR, immunofluorescence, FISH, TEM and flow cytometry. There were 427 differentially expressed genes in the LPS?stimulated MG63 cells, in which NEAT1 was significantly downregulated. LPS upregulated the expression of inflammatory cytokines and NLRP3, inhibited the expression of autophagy?related and osteogenesis?related proteins, promoted apoptosis and altered the cell cycle, which was partially inhibited by NEAT1 overexpression and promoted by bexarotene. LPS stimulated inflammation in the MG63 cells and inhibited the retinoid X receptor (RXR)?? to downregulate the expression of NEAT1 and decrease levels of autophagy, which promoted the activation of NLRP3 and the release of inflammatory factors, and impaired the functional activity of osteoblasts, thus promoting the development of inflammation.

SUBMITTER: Dai W

PROVIDER: S-EPMC7797466 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome.

Dai Wenyu W Wang Manyi M Wang Peiqi P Wen Ji J Wang Jiangyue J Cha Sa S Xiao Xueling X He Yiruo Y Shu Rui R Bai Ding D

International journal of molecular medicine 20201222 2

The mechanisms of inflammation in bone and joint tissue are complex and involve long non‑coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were sti ...[more]

PMID: 33416115

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Project description:BackgroundMitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation.MethodsReactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed.ResultsCellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells.ConclusionTaken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.

Dataset Information

LncRNA NEAT1 ameliorates LPS?induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome.

Publications

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome.

Similar Datasets

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