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Taxol, a microtubule‐stabilizing antineoplastic agent, induces expression of tumor necrosis factor α and interleukin‐1 in macrophages
Author(s) -
Bogdan Christian,
Ding Aihao
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.1.119
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , biology , cytokine , macrophage , interleukin , northern blot , microbiology and biotechnology , pharmacology , messenger rna , immunology , in vitro , biochemistry , gene
Taxol, a naturally occurring diterpene with antitumor activity, induces tubulin polymerization to generate abnormally stable and nonfunctional microtubules. Previously, we showed that taxol has lipopolysaccharide (LPS)‐like effects on macrophages. As LPS is a potent inducer of macrophage cytokine production, we investigated whether a similar effect is exerted by taxol. In a dose‐dependent manner, LPS‐free taxol induced release of biologically active tumor necrosis factor α (TNF) by inflammatory murine macrophages. Taxolinduced production of TNF was inhibitable by interleukin‐10. By Northern blot, taxol (10 and 1μM) induced TNF mRNA expression to an extent similar to LPS. Induction of TNF mRNA by 10 μM taxol was detectable at 45 min of stimulation, maximal at 90 min, and evident for at least 8 h. The same low concentration of taxol also induced interleukin 1 (IL‐1) α and β mRNA expression. We conclude that taxol triggers macrophages for TNF and IL‐1 production. These LPS‐like effects of taxol might contribute to its antitumor activity.