Microtubule-disrupting agents inhibit nitric oxide production in murine peritoneal macrophages stimulated with lipopolysaccharide or paclitaxel (Taxol)

Paclitaxel (Taxol), a yew-derived antimitotic agent which binds to microtubules, can mimic certain effects of lipopolysaccharide (LPS) on macrophages from LPS responder mouse strains. The production of nitric oxide (NO) by the peritoneal macrophages of LPS responder C3H/HeN mice stimulated with taxol or LPS was partially, but not completely, suppressed by microtubule-disrupting agents, such as colchicine, podophyllotoxin, vinblastine, and nocodazole, but not by lumicolchicine, an inactive derivative of colchicine. Inducible NO synthase protein expression induced by taxol and LPS in the macrophages was also suppressed by colchicine, but colchicine did not suppress the transcription of iNOS mRNA in the macrophages after stimulation with taxol or LPS. These findings suggest that microtubules function in the posttranscriptional processes of iNOS protein expression rather than in the transcriptional process of iNOS mRNA and the synthetic process of NO molecules.