Role of suppressor of cytokine signaling 1 in berberine mediated-inhibition of lipopolysaccharide and interferon-γ-induced N9 microglial activation / 国际脑血管病杂志

ABSTRACT

Objective:To investigate the role of suppressor of cytokine signaling 1 (SOCS1) in berberine (BBR) mediated-inhibition of microglial activation.Methods:The combination of lipopolysaccharide (LPS) and interferon-γ (IFN-γ) activated N9 microglia to mimic neuroinflammation. The cells were divided into control group, simulated neuroinflammation group (10 ng/ml LPS+ 10 U/ml IFN-γ), BBR treatment group (1 μmol/L BBR+ LPS/IFN-γ), SOCS1-siRNA treatment group (SOCS1-siRNA+ BBR+ LPS/IFN-γ), and scrambled siRNA treatment group (SC-siRNA+ BBR+ LPS/IFN-γ). After incubation for 24 h, the expression levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in cell culture medium were detected by enzyme-linked immunosorbent assay. Western blotting was used to detect the expression levels of inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB). Immunocytochemical method was used to observe cell morphology and iNOS expression.Results:Compared with the control group, LPS/IFN-γ significantly increased the levels of TNF-α and IL-6 in the medium, up-regulated the expression levels of iNOS and NF-κB (all P<0.05), and increased the volume of microglia. 1 μmol/L-BBR significantly inhibited the release of TNF-α and IL-6 from microglia, decreased the expression levels of iNOS and NF-κB (all P<0.05), and improved cell morphology. SOCS1-siRNA significantly reversed the inhibitory effect of BBR on microglia activation (all P<0.05). Conclusions:BBR may inhibit LPS and IFN-γ-induced microglial activation through SOCS1 molecule.