Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 by endotoxin-stimulated human blood monocytes.
We have reported that N-(p-coumaroyl) serotonin (CS) and its derivatives with antioxidative activity are present in safflower seeds. As reactive oxygen species (ROS) are implicated in the signaling of lipopolysaccharide (LPS), we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocytes in vitro. CS at 50-200 microM reduced tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 activities in the culture supernatants from LPS-stimulated human blood monocytes without cytotoxicity. ELISA assay revealed that the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 was inhibited by CS. Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS. NF-kappaB activation was also inhibited by CS. These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes, and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappaB activation.
Kawashima
S
S
Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Hayashi
M
M
Takii
T
T
Kimura
H
H
Zhang
H L
HL
Nagatsu
A
A
Sakakibara
J
J
Murata
K
K
Oomoto
Y
Y
Onozaki
K
K
D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species; D012639:Seeds / Q000737:chemistry; D012701:Serotonin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin