Inhibition of the expression of inducible cyclooxygenase and proinflammatouy cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases

Daniel Hwang, Nikolaus H. Fischer, Byeong C. Jang, Heekyung Tak, Jin K. Kim, Wan Lee

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

In our previous studies, it was shown that protein tyrosine kinase (PTK) inhibitors, radicicol and herbimycin A, inhibit the expression of the mitogen-inducible cyclooxygenase (COX-2) and proinflammatory cytokines. Radicicol and herbimycin A possess polarized double bonds which can conjugate sulphydryl groups of proteins. Parthenolide, the predominant sesquiterpene lactone in European feverfew (Tanacetum parthenium), contains α-methylene-gamma-lactone (MGL) and an epoxide in its structure. These moieties can interact with biological nucleophiles such as a sulfhydryl group. Parthenolide inhibited the expression of COX-2 and proinflammatory cytokines (TNFα and IL-1) in lipopolysaccharide (LPS)-stimulated macrophages. The structure-function relationship indicates that the MGL moiety confers the inhibitory effect. Parthenolide suppressed LPS-stimulated protein tyrosine phosphorylation in the murine macrophage cell line (RAW 264.7). This suppression was correlated with its inhibitory effect on the expression of COX-2 and the cytokines. Among tyrosine phosphorylated proteins, mitogen-activated protein kinases (MAPKs) exhibited the most dramatic inhibition.

Original languageEnglish (US)
Pages (from-to)810-818
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume226
Issue number3
DOIs
StatePublished - Sep 24 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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