MicroRNA-155 modulates the expression of pro-inflammatory cytokines in natural killer cells of rats exposed to chronic mild stress by regulation of ERK1/2 signaling pathway

Objectives: MicroRNAs (miRNAs) have been reported to be involved in depression. Besides, cell-mediated immunity (CMI) and inflammatory response system (IRS) are responsible for depression. The purpose of our study was to investigate the role of microRNA-155 (miR-155) in depression and the possible mechanism involving pro-inflammatory cytokines (PICs). Methods: Sprague-Dawley (SD) rats were randomly assigned to control and stress group. The rats in the stress group were subjected to chronic mild stress (CMS). Natural killer (NK) cells were isolated from peripheral blood mononuclear cells (PBMCs) of the rats in the both two groups. The expression levels of miR-155 in NK cells were determined by quantitative real-time RCP (qRT-PCR). Lentiviral vectors expressing a miR-155 sponge (Lv-miR155-sponge) and an empty vector (Lv-control) were then transfected into NK cells and confirmed by qRT-PCR. Quantitative analyses of supernatants levels for interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were performed before and after transfection using enzyme-linked immunosorbent assay (ELISA). In addition, the protein levels of phospho-extracellular signal-regulated kinase (ERK) 1/2 and ERK1/2 were evaluated after transfection. Results: The relative levels of miR-155 and PICs were significantly increased in the stress group compared to the control group. But transfection with Lv-miR155-sponge significantly decreased the levels of IL-1, IL-6, TNF-alpha, and IFN-gamma (all P<0.05) and activated ERK1/2 signaling pathway. Conclusion: Our results suggest that miR-155 modulates the expression of PICs in NK cells of rats exposed to CMS by regulation of ERK1/2 signaling pathway.