ISSN: 2576-3881

Journal of Cytokine Biology
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  • Research Article   
  • J Cytokine Biol, Vol 2(2): 117
  • DOI: 10.4172/2576-3881.1000117

Triptolide Induces Cell Damage in Lipopolysaccharide (LPS)-Treated Macrophages in an LPS-Signaling Cascade-Dependent Manner

Kiyoko Kohama, Atsushi Koike and Fumio Amano*
Laboratory of Biodefense & Regulation, Osaka University of Pharmaceutical Sciences, 4–20–1 Nasahara, Takatsuki, Osaka 569–1094, Japan
*Corresponding Author : Fumio Amano, Laboratory of Biodefense & Regulation, Osaka University of Pharmaceutical Sciences, 4–20–1 Nasahara, Takatsuki, Osaka 569–1094, Japan, Tel: +81-72-690-1054, Fax: +81-72-690-1054, Email: amano@gly.oups.ac.jp

Received Date: Aug 16, 2017 / Accepted Date: Aug 24, 2017 / Published Date: Aug 31, 2017

Abstract

Triptolide, a Chinese plant medicine from Tripterygium wilfordii Hook F, has been shown to have inhibitory effects on macrophage activities, and we recently found that it induces sudden macrophage cell death in the presence of bacterial lipopolysaccharide (LPS). In this present study, we examined precise mechanisms underlying induction of the cytotoxicity of triptolide toward macrophages in relation to the action of LPS, and thereby showed that the cytotoxic effects depended on the concentrations of both triptolide and LPS. More than 10 ng/mL LPS was necessary in combination with 300 ng/mL triptolide. However, pre-treatment with 1 ng/mL LPS for 60 min abolished the cytotoxicity induced by 100 ng/mL LPS and 300 ng/mL triptolide, showing that the cytotoxicity was regulated by LPS-tolerance. Besides, in primary macrophages obtained from mouse peritoneum, those from C3H/HeN mice, an LPS-responder, showed similar susceptibility to triptolide and LPS-induced cell damage; whereas those from C3H/HeJ mice, an LPS hypo-responder, did not, suggesting that the cytotoxic effect of triptolide was linked to the LPS/Toll-like receptor 4 (TLR4)-signaling cascade. These results suggest that the cytotoxicity of triptolide toward macrophages was regulated by the LPS-signaling cascade through both down-regulation known as LPS-tolerance and the TLR4 receptor.

Keywords: Macrophage cell death; Triptolide; Lipopolysaccharide (LPS); Apoptosis; C3H/HeN mouse; C3H/HeJ mouse

Citation: Kohama K, Koike A, Amano F (2017) Triptolide Induces Cell Damage in Lipopolysaccharide (LPS)-Treated Macrophages in an LPSSignaling Cascade-Dependent Manner. J Cytokine Biol 2: 117. Doi: 10.4172/2576-3881.1000117

Copyright: © 2017 Kohama K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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