Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases
| Autor: | Jin K. Kim, Heekyung Tak, Nikolaus H. Fischer, Daniel H. Hwang, Byeong C. Jang, Wan Lee |
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| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Male Biophysics Gene Expression Biology Biochemistry Receptor tyrosine kinase Proinflammatory cytokine Cell Line Rats Sprague-Dawley chemistry.chemical_compound Mice Structure-Activity Relationship Macrophages Alveolar Animals Parthenolide Tyrosine Enzyme Inhibitors Molecular Biology Plants Medicinal Molecular Structure Kinase Tumor Necrosis Factor-alpha Macrophages JNK Mitogen-Activated Protein Kinases Tyrosine phosphorylation Cell Biology Radicicol Rats Isoenzymes chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Enzyme Induction Calcium-Calmodulin-Dependent Protein Kinases biology.protein Cytokines Mitogen-Activated Protein Kinases Tyrosine kinase Sesquiterpenes Interleukin-1 |
| Zdroj: | Biochemical and biophysical research communications. 226(3) |
| ISSN: | 0006-291X |
| Popis: | In our previous studies (Refs. 1 and 2), 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 alpha-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 (TNF alpha 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. |
| Databáze: | OpenAIRE |
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