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

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... 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)-α, and interferon (IFN)-γ 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-α, and IFN-γ (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.