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

Int Immunopharmacol. 2004 Aug;4(8):1029-38. doi: 10.1016/j.intimp.2004.03.014.

Abstract

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 Absignificantly blocked PCSC-induced NO production activation. In conclusion, we demonstrate that PCSC induces NF-kappaB/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-kappaB/Rel activation in murine macrophages.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Electrophoretic Mobility Shift Assay
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Female
  • Lipopolysaccharide Receptors / immunology
  • Macrophage-1 Antigen / immunology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • NF-kappa B / biosynthesis*
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Oncogene Proteins v-rel / biosynthesis*
  • Polyporales*
  • Polysaccharides / pharmacology*
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Lipopolysaccharide Receptors
  • Macrophage-1 Antigen
  • NF-kappa B
  • Nitrites
  • Oncogene Proteins v-rel
  • Polysaccharides
  • Receptors, Immunologic
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases