Exopolysaccharide of Laetiporus sulphureus var. miniatus downregulates LPS-induced production of NO, PGE2, and TNF-α in BV2 microglia cells via suppression of the NF-κB pathway

Our previous study showed that the exopolysaccharide (EPS) of Laetiporus sulphureus var, miniatus was well characterized and prevented cell damage in streptozotocin-induced apoptosis. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Therefore, we attempted in this study to determine whether EPS induces a significant inhibition of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia cells. Our results showed that EPS significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E-2 (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha), without any significant cytotoxicity. EPS also downregulated mRNA and protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha in LPS-induced BV2 microglia cells. Our data also revealed that EPS treatment significantly reduced translocation of nuclear factor-kappa B (NF-kappa B) subunit p65 and its DNA-binding activity in LPS-stimulated BV2 microglia cells. Furthermore, we confirmed by using proteasome inhibitor N-acetyl-L-cysteine (NAC), that the inhibition of NF-kappa B activity influenced the expression of pro-inflammatory genes in LPS-induced BV2 microglia cells. As expected, NAC suppressed the expression of iNOS, COX-2, and TNF-alpha by blocking proteasome-mediated degradation. Taken together, our data indicate that EPS inhibits the expression of pro-inflammatory mediators by suppressing NF-kappa B activity. (C) 2011 Elsevier Ltd. All rights reserved.