5-Fluorouracil prevents lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells by inhibiting Akt-dependent nuclear factor-kappaB activation.
The effect of 5-fluorouracil (5-FU) on the production of nitric oxide (NO) in macrophages was examined by using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-FU at non-toxic concentrations significantly inhibited NO production in LPS-stimulated RAW 264.7 cells. The inhibition by 5-FU was mediated by attenuated expression of an inducible NO synthase protein and mRNA. 5-FU inhibited the activation of nuclear factor (NF)-kappaB and the subsequent nuclear translocation. Furthermore, 5-FU inhibited the phosphorylation of Akt, an upstream molecule of NF-kappaB signaling. 5-FU did not affect a series of mitogen-activated protein kinases. Therefore, 5-FU was suggested to inhibit the LPS-induced NO production in activated macrophages through preventing Akt-dependent NF-kappaB activation.
Islam
Shamima
S
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
Hassan
Ferdaus
F
Tumurkhuu
Gantsetseg
G
Ito
Hiroyasu
H
Koide
Naoki
N
Mori
Isamu
I
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C482199:lipopolysaccharide, E coli O55-B5; D009569:Nitric Oxide; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D005472:Fluorouracil