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KMID : 0379520070230010019
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한국독성학회지
2007 Volume.23 No. 1 p.19 ~ p.24
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Inhibition of NF-kB/Rel by Paclitaxel in Mouse Macrophages
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Lim Jin-Soo
Lee Seog-Ki
Jeon Young-jin
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Abstract
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We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and IFN-{gamma}-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel (>10{mu}M) has been known to induce iNOS gene expression in macrophages. However, in the previous report we described that the pretreatment of macrophages with low concentration of paclitaxel (0.1{mu}M) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited NF-kB/Rel transcriptional activation. Electrophoretic mobility shift assay further confirmed that pretreatment of macrophages with paclitaxel inhibited NF-kB/Rel DNA binding. Taxotere, a semisynthetic analog of paclitaxel, also inhibited LPS- and IFN-{gamma}-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.
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KEYWORD
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Paclitaxel, Macrophages, iNOS, NF-kB/Rel
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