Ling-Zhi-8 (LZ-8), a 13-kDa protein from mycelia of Ganoderma lucidum, exerts various beneficial functions in mammalian cells. Using murine BV-2 microglial cells, the objective of this study was to determine how LZ-8 modulates the production of pro-inflammatory mediators. Incubation of cells with LZ-8 (up to 10 µg/ml) had no negative effect on cell proliferation. LZ-8 significantly reduced the lipopolysaccharide-stimulated production of nitric oxide, prostaglandin E2 and interleukin-6 up to 31%, 39% and 58%, respectively (p <.05). LZ-8 down-regulated expression of inducible nitric oxide synthase and cyclooxygenase-2 by 69% and 37%, and also suppressed translocation of nuclear factor-kappa B (NF-κB) into the nucleus and reduced gene expression of phosphorylated NF-κB inhibitor and toll-like receptor-4 (TLR-4). In conclusion, LZ-8 reduced TLR-4-mediated NF-κB translocation into nucleus resulting in the suppression of pro-inflammatory mediator expression and production in microglial cells.
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