Upregulated TSG-6 Expression in ADSCs Inhibits the BV2 Microglia-Mediated Inflammatory Response

OBJECTIVES: The microglial cells are immune surveillance cells in the central nervous system and can be activated during neurological disorders. Adipose-derived stem cells (ADSCs) were reported to inhibit the inflammatory response in microglia by secreting proteins like tumor necrosis factor-inducible gene 6 protein (TSG-6). We aim to explore the mechanisms and the associated microRNAs. METHODS: ADSCs were cultured and TSG-6 expression was evaluated. ADSCs were cocultured with lipopolysaccharide- (LPS-) induced BV2 microglia and the supernatant was harvested for detecting cytokines. The total RNA was extracted and sequenced by high-throughput sequencing. MicroRNA profiles were compared between two treatment groups of ADSCs. A comprehensive bioinformatics analysis and confirmation experiments were performed to identify the microRNAs targeting at TSG-6. RESULTS: We found that ADSCs could secrete TSG-6 to inhibit the proinflammatory cytokines, including interleukin-1 beta and interleukin-6, and tumor necrosis factor alpha (TNFα), produced by LPS-induced microglia-mediated inflammatory response. Bioinformatics analysis showed a total of 35 microRNAs differentially expressed between the two groups of ADSCs, and miR-214-5p was identified as a regulator of TSG-6 mRNA. CONCLUSION: Following a treatment with TNFα, ADSCs can regulate the inflammatory response in LPS-activated BV2 microglia by upregulating TSG-6 expression, which itself is under the negative control of miR-214-5p.