Triptolide Attenuates Endotoxin- and Staphylococcal Exotoxin-Induced T-Cell Proliferation and Production of Cytokines and Chemokines

Abstract

Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1b, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1a, and MIP-1b by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins.

Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis

“…Coincident with our results, Lu et al found that triptolide inhibited the expression of MCP-1 in corneal fibroblasts induced by the proinflammatory cytokines IL-1β or TNF-α in a dose-dependent manner at both mRNA and protein levels [29]. Krakauer et al demonstrated that triptolide blocked the production of MCP-1 and MIP-1α by staphylococcal toxic shock syndrome toxin 1-and bacterial lipopolysaccharidestimulated human PBMC in a dose-dependent manner at both mRNA and protein levels [30]. Liu et al also found that triptolide inhibited LPS-induced DC production of MIP-1α, MCP-1, and RANTES at both mRNA and protein levels [31].…”

“…Previous studies showed triptolide inhibited nuclear translocation and the formation of the NF-κB complex [32]. Triptolide can attenuate gene expression of TNF-α, IL-1β by murine peritoneal macrophages [33] or human PBMC [30] by inhibition of nuclear NF-κB activation. Therefore, chemokines expression is inhibited subsequently.…”

Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.)

“…Many triterpene, diterpene and macrocyclic alkaloids have been isolated from this herb (Brinker et al, 2007;Ma et al, 2007). The most noteworthy component is triptolide, which has been reported to have significant antiinflammatory, immunomodulatory Krakauer et al, 2005;Liacini et al, 2005), antineoplastic (Jiang et al, 2001;Antonoff et al, 2009), and antiangiogenic properties (He et al, 2009Zhu et al, 2010). Two clinical trials in the US have shown very encouraging results (Tao et al, 2001(Tao et al, , 2002Goldbach-Mansky et al, 2009).…”

Triptolide and its expanding multiple pharmacological functions

“…Triptolide can inhibit PMA, TNF-α, or IL-1β-stimulated IL-6 and IL-8 expression by normal and transformed human bronchial epithelial cell [1], and inhibit SE-stimulated T-cell proliferation and expression of IL-1β, IL-6, TNF, IFN-γ, MCP-1, MIP-1α and MIP-1β by human PBMC [2]. Similar to human corneal fibroblasts, triptolide significantly inhibits LPS-induced expression of IL-6, G-CSF, MCP-1, IL-8, and ICAM-1 [3].…”