Triptolide attenuates oxidative stress, NF-kappaB activation and multiple cytokine gene expression in murine peritoneal macrophage.
Triptolide is a natural, biologically active compound extracted from the Chinese herb Tripterygium Wilfordii hook, that possesses potent immunosuppressive properties. In the course of our study, we examined the effects of triptolide on stimulated murine macrophages and demonstrated that triptolide inhibited superoxide anion production, NO production, and the expression of iNOS mRNA and the mRNA of some key inflammation-related cytokines, namely TNF-alpha, IL-1beta, IL-6 and IFN-gamma. This inhibition was accompanied by the inhibition of nuclear transcription factor NF-kappaB activation. We further developed a mathematical model to simulate interplay between triptolide, ROS, NF-kappaB, iNOS and related cytokines. Our results suggest that triptolide acts to regulate inflammation through NF-kappaB-mediated inhibition of inflammation-related cytokines and the production of superoxide anion and NO.
Wu
Yuanyuan
Y
State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210093, P.R. China.
Cui
Jun
J
Bao
Xiaofeng
X
Chan
Siopeng
S
Young
D Owen
DO
Liu
Dan
D
Shen
Pingping
P
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004224:Diterpenes / Q000378:metabolism*; D004852:Epoxy Compounds; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010616:Phenanthrenes / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D013481:Superoxides; C001899:triptolide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II