lignans and Streptococcal-Infections

Our previous studies have shown that Magnolol (Mag) improves the symptoms and decreases the levels of cytokines during infection induced by Streptococcus suis (S. suis) in mice. Although some reports show that Mag inhibits lipopolysaccharide-induced inflammatory responses via downregulating mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, the molecular mechanisms underlying Mag-mediated inhibition of S. suis-induced inflammatory responses are poorly understood. Here, RAW264.7 cells were stimulated with S. suis in the presence or absence of Mag. Cell viability and bactericidal effects were examined, and the concentrations of tumor necrosis factor-a (TNF-α), IL-1β (interleukin-1β), IL-6 (interleukin-6), and IL-8 (interleukin- 8) were determined by ELISA. The change in ROS (reactive oxygen species) was determined by fluorescence microscopy and ELISA. The levels of Toll-like receptor 2 (TLR2) and MAPK family proteins and NF-κB signaling were determined by Western blot analysis. S. suis induced massive RAW264.7 cell death, a decline in bactericidal activity, the release of inflammatory cytokines, increased oxidative stress, and activation of TLR2/MAPK/NF-κB signaling pathways. Mag treatment significantly suppressed macrophage cell death and caused a decline in bactericidal activity. Furthermore, Mag decreased inflammatory cytokines production and ROS generation. It also prevented p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), inhibitor of NF-κB (IκB), and NF-κB phosphorylation induced by S. suis in a dose-dependent manner. Our results indicate that Mag exerts anti-inflammatory and cell-protective effects and mediates the activation of MAPK and NF-κB signaling by downregulating the expression of TLR2 upregulated by S. suis.

Topics: Animals; Anti-Bacterial Agents; Biphenyl Compounds; Gene Expression Regulation; Lignans; Mice; Mitogen-Activated Protein Kinase Kinases; Molecular Structure; NF-kappa B; RAW 264.7 Cells; Reactive Oxygen Species; Streptococcal Infections; Streptococcus suis; Toll-Like Receptor 2