Piceatannol prevents lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor (NF)-kappaB activation by inhibiting IkappaB kinase (IKK).
The effect of piceatannol on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was examined. Piceatannol significantly inhibited NO production in LPS-stimulated RAW 264.7 cells. The inhibition was due to the reduced expression of an inducible isoform of NO synthase (iNOS). The inhibitory effect of piceatannol was mediated by down-regulation of LPS-induced nuclear factor (NF)-kappaB activation, but not by its cytotoxic action. Piceatannol inhibited IkappaB kinase (IKK)-alpha and beta phosphorylation, and subsequently IkappaB-alpha phosphorylation in LPS-stimulated RAW 264.7 cells. On the other hand, piceatannol did not affect activation of mitogen-activated protein (MAP) kinases including extracellular signal regulated kinase 1/2 (Erk1/2), p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Piceatannol inhibited the phosphorylation of Akt and Raf-1 molecules, which regulated the activation of IKK-alpha and beta phosphorylation. The detailed mechanism of the inhibition of LPS-induced NO production by piceatannol is discussed.
Islam
Shamima
S
Department of Microbiology and Immunology and Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Hassan
Ferdaus
F
Mu
Mya Mya
MM
Ito
Hiroyasu
H
Koide
Naoki
N
Mori
Isamu
I
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D000818:Animals; D002460:Cell Line; D051550:I-kappa B Kinase; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; D009569:Nitric Oxide; C041525:3,3',4,5'-tetrahydroxystilbene; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases