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| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 1(3):267-282;2009
Original Article
Triptolide induces anti-inflammatory cellular responses
Ranyia Matta, Xianxi Wang, Hui Ge, William Ray, Leif D. Nelin, Yusen Liu
From the Integrated Biomedical Science Graduate Program, the Centers for Perinatal Research and Microbial
Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Department of Pediatrics, The Ohio
State University College of Medicine, Columbus, Ohio 43205, and ProteinOne, Bethesda, Maryland 20814
Received March 6, 2009; accepted March, 2009; available online March, 2009
Abstract: Tripterygium wilfordii Hook F. has been used for centuries in traditional Chinese medicine to treat
rheumatoid arthritis, an autoimmune disease associated with increased production of the pro-inflammatory
cytokine, tumor necrosis factor (TNF)2-α. Triptolide is a compound originally purified from T. wilfordii Hook F. and
has potent anti-inflammatory and immunosuppressant activities. In this study, we investigated the effect of
triptolide on the global gene expression patterns of macrophages treated with lipopolysaccharide (LPS). We
found that LPS stimulation resulted in >5-fold increase in expression of 117 genes, and triptolide caused a >50%
inhibition in 47 of the LPS-inducible 117 genes. A large portion of the genes that were strongly induced by LPS
and significantly inhibited by triptolide were pro-inflammatory cytokine and chemokine genes, including TNF-α, IL-
1β, and IL-6. Interestingly, LPS also induced the expression of micro-RNA-155 (miR-155) precursor, BIC, which
was inhibited by triptolide. Confirming the cDNA array results, we demonstrated that triptolide blocked the
induction of these proinflammatory cytokines as well as miR-155 in a dose-dependent manner. Profound
inhibition of pro-inflammatory cytokine expression was observed at concentrations as low as 10-50 nM.
However, triptolide neither inhibited the phosphorylation or degradation of IκBα after LPS stimulation, nor affected
the DNA-binding activity of NF-κB. Surprisingly, we found that triptolide not only inhibited NF-κB-regulated reporter
transcription, but also dramatically blocked the activity of other transcription factors. Our study offers a plausible
explanation of the therapeutic mechanism of T. wilfordii Hook F. (AJTR903001).
Key Words: Inflammation, cytokines, transcription, Chinese medicine, rheumatoid arthritis, Tripterygium wilfordii
Full Text PDF
Address all correspondence to:
Yuseng Liu,PhD
Center for Perinatal Research
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive
Columbus, OH 43205
USA.
Tel: (614) 722-3073; Fax: (614) 355-3455
E-mail: yusen.liu@nationwidechildrens.org
Original Article
Triptolide induces anti-inflammatory cellular responses
Ranyia Matta, Xianxi Wang, Hui Ge, William Ray, Leif D. Nelin, Yusen Liu
From the Integrated Biomedical Science Graduate Program, the Centers for Perinatal Research and Microbial
Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Department of Pediatrics, The Ohio
State University College of Medicine, Columbus, Ohio 43205, and ProteinOne, Bethesda, Maryland 20814
Received March 6, 2009; accepted March, 2009; available online March, 2009
Abstract: Tripterygium wilfordii Hook F. has been used for centuries in traditional Chinese medicine to treat
rheumatoid arthritis, an autoimmune disease associated with increased production of the pro-inflammatory
cytokine, tumor necrosis factor (TNF)2-α. Triptolide is a compound originally purified from T. wilfordii Hook F. and
has potent anti-inflammatory and immunosuppressant activities. In this study, we investigated the effect of
triptolide on the global gene expression patterns of macrophages treated with lipopolysaccharide (LPS). We
found that LPS stimulation resulted in >5-fold increase in expression of 117 genes, and triptolide caused a >50%
inhibition in 47 of the LPS-inducible 117 genes. A large portion of the genes that were strongly induced by LPS
and significantly inhibited by triptolide were pro-inflammatory cytokine and chemokine genes, including TNF-α, IL-
1β, and IL-6. Interestingly, LPS also induced the expression of micro-RNA-155 (miR-155) precursor, BIC, which
was inhibited by triptolide. Confirming the cDNA array results, we demonstrated that triptolide blocked the
induction of these proinflammatory cytokines as well as miR-155 in a dose-dependent manner. Profound
inhibition of pro-inflammatory cytokine expression was observed at concentrations as low as 10-50 nM.
However, triptolide neither inhibited the phosphorylation or degradation of IκBα after LPS stimulation, nor affected
the DNA-binding activity of NF-κB. Surprisingly, we found that triptolide not only inhibited NF-κB-regulated reporter
transcription, but also dramatically blocked the activity of other transcription factors. Our study offers a plausible
explanation of the therapeutic mechanism of T. wilfordii Hook F. (AJTR903001).
Key Words: Inflammation, cytokines, transcription, Chinese medicine, rheumatoid arthritis, Tripterygium wilfordii
Full Text PDF
Address all correspondence to:
Yuseng Liu,PhD
Center for Perinatal Research
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive
Columbus, OH 43205
USA.
Tel: (614) 722-3073; Fax: (614) 355-3455
E-mail: yusen.liu@nationwidechildrens.org
