Activation of mitogen-activated protein kinase pathways by angelan in murine macrophages

Young Jin Jeon, Sang Bae Han, Sang Han Lee, Hyoung Chin Kim, Kyung Seop Ahn, Hwan Mook Kim

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, specifically activated macrophages to induce cytokines including inducible nitric oxide synthase (iNOS) which has strong anti-tumor activities [Immunopharmacology, 1999; 43: 1.]. In the present study, we investigated the intracellular signal transduction pathways involved in the angelan-induced iNOS synthesis by murine macrophages. Protein tyrosine phosphorylation was induced within 5 min by angelan, and the blocking of protein tyrosine kinases (PTKs) inhibited down-stream pathways leading to iNOS production in response to angelan. Treament of RAW 264.7 cells with angelan resulted in significant activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced iNOS synthesis, whereas the selective mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the iNOS induction. In conclusion, we demonstrate that PTK and p38 MAPK activation are required to transduce signals leading to iNOS expression in angelan-stimulated murine macrophages.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalInternational Immunopharmacology
Volume1
Issue number2
DOIs
StatePublished - Mar 12 2001

Keywords

  • Angelan
  • Angelica gigas Nakai
  • Macrophages
  • PTK
  • p38

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