MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression related to inflammatory responses. Human adipose stem cells are characterized by pluripotent differentiation potential and isolated from adipose tissues. These cells regulate inflammation mainly by interacting with immune cells and affecting the secretion of immune factors; details of this interaction are currently unknown. In the current study, we successfully established an acute inflammation model and a chronic inflammation model involving adipose stem cells. We used high-throughput miRNA microarray analysis to identify miRNAs that were significantly (p < 0.05) differentially expressed during both acute and chronic inflammation. Lipopolysaccharide (LPS) significantly (p < 0.05) reduced the expression of miR-223-3P and miR-2909, while promoting the production of pro-inflammatory cytokines, interleukin (IL) 6, IL-1β, and tumor necrosis factor (TNF)-α via the Toll-like receptor (TLR) 4/TLR2/nuclear factor (NF)-κB/signal transducer and activator of transcription (STAT) 3 signaling pathway in human adipose stem cells. Further, miR-223-3P expression was significantly (p < 0.05) reduced in human adipose stem cells during activation by IL-6 stimulation. The inducible down-regulation of miR-223-3P resulted in the activation of STAT3, which was directly targeted by miR-223-3P. STAT3 directly targeted TLR4 and TLR2, promoting the production of the pro-inflammatory cytokine, IL-6, and formed a positive feedback loop to regulate IL-6 levels. Similarly, TNF-α significantly (p < 0.05) increased the expression of miR-223-3p, with LPS and TLR4/TLR2/NF-κB/STAT3 forming a negative feedback loop to regulate TNF-α levels. In addition, miR-2909, which depends on NF-κB, targeted Krueppel-like factor (KLF) 4 to regulate the levels of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α. We conclude that miR-223-3p and miR-2909 form a complex regulatory network with pro-inflammatory factors and signaling pathways in adipose stem cells stimulated by LPS. These findings will inform the development of therapies against autoimmune and inflammatory diseases.

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Toxoplasma gondii (T. gondii) infection is a risk factor for the development of some neuropsychiatric diseases. 1 Numerous clinical studies have shown that the seroprevalence of T. gondii is associated with a variety of neuropsychiatric conditions, including schizophrenia, 2 suicidal behaviour, 2 mixed anxiety and depressive disorder. [3][4][5][6][7] T. gondii infection affects the predisposition and severity of depression in children and adolescents. 8 In our recent study, mice were also found to exhibit depression-like behaviours in a mouse model of T. gondii infection 9 or in offspring of mice with maternal T. gondii infection during pregnancy. 10 However, another study did not find a relationship between toxoplasmosis and major depression disorder. 11 Numerous studies have explored the causes of this controversy, that is, whether T. gondii infection induces mental disorder and whether this is affected by the host genetic susceptibility, 12 age of first exposure to T. gondii, 13 T. gondii strain 14 and symptom severity. 15 Interestingly, a case report of a T. gondii-seropositive depressed patient has shown that antidepressant treatment can be improved only after appropriate treatment for toxoplasmosis. 16 Thus, further research is required to examine the correlation between T. gondii infection and depression-like behaviours, to elucidate the exact mechanisms of depression-like behaviours caused by T. gondii infection, and to identify suitable drugs for treatment.