EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages

Historically, consumption of Green tea (Camellia sinensis) has been associated with health benefits against multiple diseases including cancer, atherosclerosis and cardiovascular disorders. Emerging evidence has suggested a pathogenic role for HMGB1, a newly identified "late" mediator of lethal systemic inflammation, in the aforementioned diseases. Here we demonstrated that a major ingredient of Green tea, EGCG, was internalized into HMGB1-containing LC3-positive cytoplasmic vesicles (likely autophagosomes) in macrophages, and induced HMGB1 aggregation in a time-dependent manner. Furthermore, EGCG stimulated LC3-II production and autophagosome formation, and inhibited LPS-induced HMGB1 up-regulation and extracellular release. The EGCG-mediated HMGB1 inhibitory effects were diminished by inhibition of class III phosphatidylinositol-3 kinase (with 3-methyladenine) or knockdown of an essential autophagy-regulating protein, beclin-1. Moreover, the EGCG-mediated protection against lethal sepsis was partly impaired by co-administration of an autophagy inhibitor, chloroquine. Taken together, the present study has suggested a possibility that EGCG inhibits HMGB1 release by stimulating its autophagic degradation.

Li, Wei
Zhu, Shu
Li, Jianhua
Assa, Andrei
Jundoria, Arvin
Xu, Jianying
Fan, Saijun
Eissa, N. Tony
Tracey, Kevin J.
Sama, Andrew E.
Wang, Haichao
Item Type: 
Journal Article
Publication Title: 
Biochemical Pharmacology
Journal Abbreviation: 
Biochem. Pharmacol.
Publication Date: 
May 1, 2011
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 21371444 PMCID: PMC3072446

Turabian/Chicago Citation

Wei Li, Shu Zhu, Jianhua Li, Andrei Assa, Arvin Jundoria, Jianying Xu, Saijun Fan, N. Tony Eissa, Kevin J. Tracey, Andrew E. Sama and Haichao Wang. May 1, 2011. "EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages." Biochemical Pharmacology 81: 9: 1152-1163. 10.1016/j.bcp.2011.02.015.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.bcp.2011.02.015 | issn = 1873-2968 | volume = 81 | pages = 1152-1163 | last = Li | first = Wei | coauthors = Zhu, Shu, Li, Jianhua, Assa, Andrei, Jundoria, Arvin, Xu, Jianying, Fan, Saijun, Eissa, N. Tony, Tracey, Kevin J., Sama, Andrew E., Wang, Haichao | title = EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages | journal = Biochemical Pharmacology | date = May 1, 2011 | pmid = | pmc = }} </ref>