Inhibition of NF-kB/Rel by Paclitaxel in Mouse Macrophages

Abstract

We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and <TEX>$IFN-{\gamma}$</TEX>-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel (<TEX>$>10{\mu}M$</TEX>) 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 (<TEX>$0.1{\mu}M$</TEX>) 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 <TEX>$IFN-{\gamma}$</TEX>-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.