Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase.
Triptolide (PG490) is a natural, biologically active compound extracted from the Chinese herb Tripterygium wilfordii. It has been shown to possess potent anti-inflammatory and immunosuppressive properties. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, triptolide inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which triptolide inhibits murine iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAP kinases) and nuclear factor-kappa B (NF-kappa B) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH(2)-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, triptolide significantly inhibited the DNA binding activity of NF-kappa B. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-kappa B and JNK activation.
Kim
Young-Ho
YH
Department of Immunology, School of Medicine, Keimyung University, 194 Dong San-Dong Jung-Gu, Taegu 700-712, South Korea.
Lee
Sang-Han
SH
Lee
Jai-Youl
JY
Choi
Sang-Won
SW
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D000818:Animals; D002460:Cell Line; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*
D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases