Triptolide inhibits COX-2 expression via NF-kappa B pathway in astrocytes.
Previous investigations have showed that triptolide possessed potent anti-inflammatory and immunosuppressive properties. In the present study, we examined the protective effects of triptolide on the inflammatory response induced by bacterial lipopolysaccharide (LPS) both in vivo and in vitro. Intrahippocampal injection of LPS (4 microg) in rats significantly increased the immunoreactivity of glial fibrillary acid protein (GFAP) and cyclooxygenase-2 (COX-2) in the injected region, which was reduced by pretreatment with triptolide (10-50 microg/kg) for 5d. In the cultured human differentiated A172 astroglial cells, LPS (1mg/L) increased the expression of COX-2 mRNA and protein, the production of prostaglandin E(2) (PGE(2)) and the DNA binding activity of NF-kappa B, which were markedly attenuated by pretreatment with triptolide (0.2-5 microg/L) for 1h. These results suggested that the protective effect of triptolide on neuroinflammation is mediated by decreasing COX-2 expression, at least partly, via the inhibition of NF-kappa B signaling pathway.
Dai
Yu-Qiao
YQ
Department of Anatomy and Neurobiology, Xiang-Ya School of Medicine, Central South University, Changsha 410013, China.
Jin
Dao-Zhong
DZ
Zhu
Xing-Zu
XZ
Lei
De-Liang
DL
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds; D015870:Gene Expression / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone