A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- κ B and NF- κ B-mediated cellular FLICE-inhibitory protein

Acta Pharmaceutica Sinica. B
Ziqiao YuanLuyong Zhang

Abstract

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF-α inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF-α by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-α to assess the function of TNF-α in TP/LPS co-treatment. Additionally, time-dependent NF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro. Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-κB-mediated pro-survival protein, was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-α, revealing the role of TNF-α in TP/LPS-induced hepatotoxicity. Mechanistic stud...Continue Reading

References

Apr 1, 1976·Mutation Research·O L Klamerth
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Jul 21, 2001·Molecular and Cellular Biology·O MicheauJ Tschopp
Nov 20, 2001·Molecular and Cellular Biology·A KruegerS Kirchhoff
Mar 5, 2002·Nature Immunology·Michael Karin, Anning Lin
Jul 20, 2002·Biochemical and Biophysical Research Communications·Hyun A Kim, Yeong W Song
Jan 29, 2003·Journal of Virology·Denise Perez, Eileen White
Aug 2, 2003·The Journal of Pharmacology and Experimental Therapeutics·James P LuyendykRobert A Roth
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Dec 25, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael J LiguoriJeffrey F Waring
Sep 19, 2006·Journal of Hepatology·Christian Liedtke, Christian Trautwein
Aug 19, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Francis F TukovRobert A Roth
Aug 22, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Patrick J ShawRobert A Roth
May 20, 2008·Cell·Lai WangXiaodong Wang
Mar 24, 2009·Annual Review of Immunology·Ian Nicholas Crispe
Apr 11, 2009·Gut·A MencinR F Schwabe
Jul 30, 2009·The Journal of Pharmacology and Experimental Therapeutics·Wei ZouPatricia E Ganey
Dec 30, 2009·The Journal of Cell Biology·Peter GeserickMartin Leverkus
Sep 4, 2010·Journal of Hepatology·Maria L OllerosIrene Garcia
Oct 26, 2010·Nature Reviews. Immunology·Angus W Thomson, Percy A Knolle
Jun 28, 2011·Journal of Hepatology·Jörn M SchattenbergMarcus Schuchmann
Jul 21, 2011·Nature Immunology·Andrea OeckinghausSankar Ghosh
Aug 3, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang LiHong-Yang Wang
Oct 11, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jingtao LuPatricia E Ganey
Feb 14, 2012·The EMBO Journal·Maryline MoulinDavid L Vaux
Dec 20, 2012·Science Signaling·Xuehua PiaoHiroyasu Nakano
Jan 16, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sanjoy RoychowdhuryLaura E Nagy
Mar 12, 2013·Pharmacological Reviews·Jack Uetrecht, Dean J Naisbitt
May 4, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jiaying WangLuyong Zhang
Jan 22, 2014·Fitoterapia·Xinzhi WangLuyong Zhang
Jun 17, 2014·Journal of Ethnopharmacology·Xiao-Jiaoyang LiLu-yong Zhang
Dec 24, 2015·International Journal of Molecular Sciences·Yuichi TsuchiyaHiroyasu Nakano
Feb 16, 2016·Trends in Cell Biology·Nieves PeltzerHenning Walczak
Jul 18, 2016·Trends in Immunology·Adrian T Ting, Mathieu J M Bertrand
Sep 9, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jo SudaZhang-Xu Liu
Nov 2, 2016·The Journal of Clinical Investigation·Claudia GüntherStefan Wirtz

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Citations

May 14, 2021·Journal of Cellular and Molecular Medicine·Ji-Min DaiJing-Yao Dai
Jul 13, 2021·Immunological Investigations·Cong WangMing Xu
Nov 17, 2021·Immunopharmacology and Immunotoxicology·Cong WangMing Xu

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Methods Mentioned

BETA
transfection
Assay
ubiquitination

Software Mentioned

GraphPad Prism
Image J

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