title: Triptolide inhibits COX-2 expression and PGE2 release by suppressing the activity of NF-kappaB and JNK in LPS-treated microglia.
abstract: Activated microglia participate in neuroinflammation which contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglial activation may have potential anti-inflammatory effects. Our laboratory has previously reported that triptolide, a natural biologically active compound extracted from Tripterygium wilfordii, could protect dopaminergic neurons from inflammation-mediated damage. However, the mechanism by which triptolide inhibits inflammation remains unknown. We reported here that inhibition of prostaglandin E(2) (PGE(2)) production could be a potential mechanism of triptolide to suppress inflammation. Triptolide suppressed c-jun NH2-terminal kinase (JNK) phosphorylation, cyclooxygenase 2 (COX-2) expression and PGE(2) production in microglial cultures treated with lipopolysaccharide (LPS). Triptolide also greatly inhibited the transcriptional activity, but not the DNA-binding activity of nuclear factor-kappaB (NF-kappaB) in microglia following LPS stimulation. These results indicate that triptolide might suppress NF-kappaB activity to down-regulate COX-2 expression. The LPS-stimulated transcriptional activity of NF-kappaB was suppressed by inhibition of p38MAPK, but not by that of JNK and extracellular signal-regulated kinase. Furthermore, the LPS-induced PGE(2) production was reduced by inhibiting these kinases. Taken together, these results suggest that triptolide may suppress neuroinflammation via a mechanism that involves inactivation of two parallel signaling pathways: p38-NF-kappaB-COX-2-PGE(2) and JNK-PGE(2).
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Ministry of Education, Key Laboratory for Neuroscience, Beijing, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Gong
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.forename: Jian
authors.initials: J
authors.lastname: Jiao
authors.forename: Liming
authors.initials: L
authors.lastname: Jing
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang