Nystatin-induced nitric oxide production in mouse macrophage-like cell line RAW264.7.
Nystatin is known to deplete lipid rafts from mammalian cell membranes. Lipid rafts have been reported to be necessary for lipopolysaccharide signaling. In this study, it was unexpectedly found that lipopolysaccharide-induced nitric oxide production was not inhibited, but rather increased in the presence of a non-cytotoxic concentration of nystatin. Surprisingly, treatment with nystatin induced only NO production and iNOS expression in RAW264.7 cells. At the concentration used, no changes in the expression of GM1 ganglioside, a lipid raft marker on RAW264.7 cells, was seen. From studies using several kinds of inhibitors for signaling molecules, nystatin-induced NO production seems to occur via the ikappaB/NF-kappaB and the PI3 K/Akt pathway. Furthermore, because nystatin is known to activate the Na-K pump, we examined whether the Na-K pump inhibitor amiloride suppresses nystatin-induced NO production. It was found that amiloride significantly inhibited nystatin-induced NO production. The results suggest that a moderate concentration of nystatin induces NO production by Na-pump activation through the PI3 kinase/Akt/NF-kappaB pathway without affecting the condition of lipid rafts.
Koide
Naoki
N
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. koide@aichi-med-u.ac.jp
Naiki
Yoshikazu
Y
Morikawa
Akiko
A
Tumurkhuu
Gantsetseg
G
Dagvadorj
Jargalsaikhan
J
Noman
Abu Shadat Mohammod
AS
Iftekar-E-Khuda
Imtiaz
I
Komatsu
Takayuki
T
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D000818:Animals; D002460:Cell Line; D005732:Gangliosides / Q000276:immunology; D051550:I-kappa B Kinase / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology*; D009761:Nystatin / Q000494:pharmacology*; D015398:Signal Transduction
D005732:Gangliosides; D016328:NF-kappa B; D009761:Nystatin; D009569:Nitric Oxide; D051550:I-kappa B Kinase