Enhancement of nitric oxide synthase induction in alveolar macrophages by in vivo administration of docetaxel.
Effects of docetaxel, a taxane-derivative anti-cancer drug, on lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis were investigated in alveolar macrophages isolated from rats. LPS-induced NO production and inducible NO synthase (iNOS) expression were significantly enhanced in the macrophages isolated from rats injected intraperitoneally with docetaxel (4 mg/kg body weight per day for 5 consecutive days) compared with those in macrophages from control rats administrated a vehicle. In vivo administration of docetaxel augmented LPS-induced p38 activation but not extracellular signal-related kinase (ERK) activation in isolated macrophages. On the other hand, in vitro treatment of macrophages with docetaxel (5 and 10 microg/ml) inhibited LPS-induced NO production and iNOS expression. Levels of lactate dehydrogenase released from macrophages were neither affected by in vitro treatment with docetaxel (up to 10 microg/ml) nor by its in vivo administration. These results suggest that docetaxel has an enhancing action in vivo on LPS-induced iNOS expression and subsequent NO production through stimulation of p38 activity in alveolar macrophages.
Saito
Fumiaki
F
Department of Hygiene and Preventive Medicine, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Matsusaka
Satoshi
S
Takahashi
Yuji
Y
Wakabayashi
Ichiro
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D043823:Taxoids; D000077143:Docetaxel; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases