Polysaccharide isolated from Poria cocos sclerotium induces NF-κB/Rel activation and NOS expression through the activation of p38 kinase in murine macrophages

in our previous studies, we showed that PCSC, a polysaccharide isolated from Poria cocos, activated macrophages to induce the translocation of NF-kappaB/Rel into nucleus and DNA binding to its cognate site in the promoter of iNOS gene [Int. Immunopharmacol. 3 (2003) 1353]. In the present study, we investigated the role of p38 kinase pathway and membrane receptors (CD14, Toll-like receptor 4 (TLR4), and CR3) in mediating nitric oxide (NO) production and NF-kappaB/Rel activation induced by PCSC. Treament of RAW 264.7 cells with PCSC resulted in significant activation of p38. The specific p38 inhibitor SB203580 abrogated the PCSC-induced NF-kappaB/Rel activation and NO generation, whereas the selective mitogen-activated protein kinase/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the NF-kappaB/Rel and NO induction. Treatment of RAW 264.7 cells with anti-CD14 Ab, anti-TLR4 Ab, and anti-CR3 Ab significantly blocked PCSC-induced NO production activation. In conclusion, we demonstrate that PCSC induces NF-KB/Rel activation and iNOS expression through the CD14, TLR4, and CR3 membrane receptor and p38 kinase which is critically involved in the signal transduction leading to NF-KB/Rel activation in murine macrophages. (C) 2004 Elsevier B.V. All rights reserved.