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

Kun Yeong Lee, Ho Jin You, Hye Gwang Jeong, Jong Soon Kang, Hwan Mook Kim, Sang Dal Rhee, Young Jin Jeon

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

In our previous studies, we showed that PCSC, a polysaccharide isolated from Poria cocos, activated macrophages to induce the translocation of NF-κB/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-κB/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-κB/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-κB/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-κB/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-κB/Rel activation in murine macrophages.

Original languageEnglish (US)
Pages (from-to)1029-1038
Number of pages10
JournalInternational Immunopharmacology
Volume4
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant R05-2002-000-01323-0 from Korea Science and Engineering Foundation.

Keywords

  • Macrophages
  • NF-κB/Rel
  • Poria cocos
  • iNOS
  • p38 kinase

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