Epigallocatechin-3-gallate ameliorates lipopolysaccharide induced acute thymus involution in mice via AMPK/Sirt1 pathway

Abstract

Abstract The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to ageing, inflammation and oxidation. Eepigallocatechin-3-gallate (EGCG) has been proven to possess the anti-inflammatory, anti-oxidant and anti-tumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria. Methodology included in vivo experiment on female kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, the immunohistochemical detection, thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and SOD levels, and decreased MDA and ROS levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator (Aire), sex determining region Y-box2 (Sox2) and nanog homebox (Nanog), and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/ Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using appropriate adjuvant natural agents. EGCG might be considered as a potential agent for the prevention and treatment of thymic involution.