Abstract
BackgroundTriptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties.ResultsHere we report the expression profile of immune signaling genes modulated by triptolide in LPS induced mouse macrophages. In an array study triptolide treatment modulated expression of 22.5% of one hundred and ninety five immune signaling genes that included Toll-like receptors (TLRs). TLRs elicit immune responses through their coupling with intracellular adaptor molecules, MyD88 and TRIF. Although it is known that triptolide inhibits NFκB activation and other signaling pathways downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. In this study, we show that triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. Also, the suppressive effect of triptolide on TLR-induced NFκB activation was observed when either MyD88 or TRIF was knocked out, confirming that both MyD88 and TRIF mediated NFκB activation may be inhibited by triptolide. Within the TLR cascade triptolide downregulates TLR4 and TRIF proteins.ConclusionsThis study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may downregulate NFκB activation during inflammatory conditions.
Highlights
Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties
Gene array data confirmed known and revealed unknown genes affected by triptolide Expression of one hundred and ninety five target genes in response to triptolide treatment were studied by gene array in LPS stimulated mouse macrophages
Huang et al (2006) reported that 320 genes were upregulated in RAW 264.7 cells in response to LPS treatment but only 32 (10%) genes were downregulated by triptolide [19]
Summary
Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties. Chronic inflammation is an important patho-physiological condition impacting various diseases including rheumatoid arthritis (RA), atherosclerosis, diabetes, and cancer. Recent evidence suggests the involvement of Tolllike receptors (TLRs) in various chronic inflammatory and autoimmune diseases [1,2,3]. TLRs belong to the family of pathogen-associated molecular pattern recognition receptors and are vital components of the host's immune system for sensing dangerous pathogens, and for initiating inflammatory and immune responses directed against these pathogens. There are two possible routes for mediation of signals received by TLRs. Triptolide is a biologically active diterpene triepoxide from a Chinese herb Tripterygium wilfordii Hook F, commonly known as thunder god vine.
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