Down Regulation of HMGB1-RAGE pathway by Ethyl Pyruvate

Abstract

HMGB1 (high Mobility Group Box 1) protein is released by nuclear after that binds to DNA. HMGB1 can also be secreted from cells, it can bind receptor for advanced glycation end products (RAGE) that inflammatory receptor. Interaction between HMGB1 and RAGE causes upregulation of NF-kB that leads to increased production of cytokines. Ethyl pyruvate (EP) is the ethyl ester of pyruvic acid. In recent research, EP has shown HMGB1 inhibitory effecting in many inflammation-related diseases through pathway inhibition. In this study, we measured that expression of HMGB1 mRNA and proteins stimulated by LPS in presence of ethyl pyruvate (EP) or other inflammatory stimulants was measured as RT-qPCR and immunoblotting analysis in BMDMs. Furthermore, levels of cytokine in the supernatant of BMDM stimulated by LPS in presence of EP or other inflammatory stimulants or mouse serum were measured by ELISA. Here in we found that EP inhibits HMGB1 pathway leading to reduced RAGE expression and NF-κB activation. Moreover, we demonstrated EP reduced HMGB1 in serum levels of mice. Our results suggested that EP is effective inhibitors of HMGB1/RAGE signaling pathway, offering a novel potential therapeutic approach to patients and HMGB1 has been proposed as a target for inflammatory disease.