Inhibition of High Mobility Group Box 1–Toll-Like Receptor-4 Signaling by Glycyrrhizin Contributes to the Attenuation of Cold Ischemic Injury of Liver in a Rat Model

2016 ◽  
Vol 48 (1) ◽  
pp. 191-198 ◽  
Author(s):  
S. Su ◽  
J. Wu ◽  
T. Gong ◽  
K. He ◽  
C. Feng ◽  
...  
2016 ◽  
Vol 38 (6) ◽  
pp. 2139-2151 ◽  
Author(s):  
Won Seok Yang ◽  
Nam Jeong Han ◽  
Jin Ju Kim ◽  
Mee Jeong Lee ◽  
Su-Kil Park

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.


2012 ◽  
Vol 18 (12) ◽  
pp. 1509-1518 ◽  
Author(s):  
Eileen M Bauer ◽  
Richard Shapiro ◽  
Han Zheng ◽  
Ferhaan Ahmad ◽  
David Ishizawar ◽  
...  

2009 ◽  
Vol 285 (7) ◽  
pp. 4995-5002 ◽  
Author(s):  
Shipan Dai ◽  
Chhinder Sodhi ◽  
Selma Cetin ◽  
Ward Richardson ◽  
Maria Branca ◽  
...  

2012 ◽  
Vol 181 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Yuji Nadatani ◽  
Toshio Watanabe ◽  
Tetsuya Tanigawa ◽  
Hirohisa Machida ◽  
Hirotoshi Okazaki ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document