Immunosuppressant PG490 (Triptolide) Inhibits T-cell Interleukin-2 Expression at the Level of Purine-box/Nuclear Factor of Activated T-cells and NF-κB Transcriptional Activation

Qiu, Daoming; Zhao, Guohua; Aoki, Yosuke; Shi, Lingfang; Uyei, A.; Nazarian, Saman; Ng, J.; Kao, Peter N.

doi:10.1074/jbc.274.19.13443

Cited by 255 publications

(230 citation statements)

References 41 publications

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“…For example, PG490 (pure triptolide, a diterpene triepoxide) is an immunosuppressant molecule that can synergize with CsA to inhibit transcriptional activation by NF-kB. However, PG490 does not appear to interfere with the induction of NF-kB DNA binding, suggesting that it acts to inhibit transcriptional activation by NF-kB (Qiu et al, 1999). Moreover, the immunosuppressant deoxyspergualin inhibits NF-kB nuclear translocation by a mechanism involving the heat-shock protein Hsp70 (Tepper et al, 1995).…”

Section: Immunosuppressive Agentsmentioning

confidence: 99%

“…Some inhibit NF-kB nuclear translocation by stabilizing IkBa (Meyer et al, 1997), some may act on NF-kB through inhibiting calcineurin (Frantz et al, 1994), some by binding heatshock proteins (Tepper et al, 1995) and some by modulating the DNA binding or transactivation potential of NF-kB (McCaffrey et al, 1994;Wechsler et al, 1994;Kunz et al, 1995;Qiu et al, 1999).…”

Section: Immunosuppressive Agentsmentioning

confidence: 99%

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Inhibitors of NF-κB signaling: 785 and counting

2006

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Section: Immunosuppressive Agentsmentioning

confidence: 99%

Section: Immunosuppressive Agentsmentioning

confidence: 99%

Inhibitors of NF-κB signaling: 785 and counting

2006

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“…Consistent with the effect on the proinflammatory signals, extracts strongly inhibited proliferation of T and B cells (Tao et al, 1991(Tao et al, , 1995. Pure triptolide (1) also inhibited T cell proliferation and production of TNF-α, IL-1, IL-2, IL-6, and IL-8 (Tao et al, 1995;Chan et al, 1999;Qiu et al, 1999;Lin et al, 2001a;Zhou et al, 2003). The suppression of metabolic activity in T cells was not due solely to reduction in cell viability (Chan et al, 1999).…”

Section: Antiinflammatory and Autoimmune Conditionsmentioning

confidence: 99%

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

et al. 2007

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Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook. f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

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“…For example, PG490 (pure triptolide, a diterpene triepoxide) is an immunosuppressant molecule that can synergize with CsA to inhibit transcriptional activation by NF-kB. However, PG490 does not appear to interfere with the induction of NF-kB DNA binding, suggesting that it acts to inhibit transcriptional activation by NF-kB (Qiu et al, 1999). Morever, the immunosuppressant deoxyspergualin inhibits NFkB nuclear translocation by a mechanism involving the heat shock protein hsp70 (Tepper et al, 1995).…”

Section: Immunosuppressive Agentsmentioning

confidence: 99%