A novel moonlight function of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for immunomodulation

Toshiaki Nakano*, Shigeru Goto, Yuki Takaoka, Hui Peng Tseng, Takashi Fujimura, Seiji Kawamoto, Kazuhisa Ono, Chao Long Chen

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related enzyme, which generates NADH in glycolysis. Our previous study revealed a novel role of exogenous GAPDH in the amelioration of lipopolysaccharide (LPS)-induced sepsis-related, severe acute lung injury (ALI) in mice. Here, we show the effect of extracellular GAPDH on the physiological functions of macrophages, which play an important role in the onset of sepsis and ALI. GAPDH has no effect on cell viability, while it strongly suppressed cell adhesion, spreading, and phagocytic function of LPS-stimulated macrophages. GAPDH treatment significantly reduced tumor necrosis factor (TNF)-α, while it induced interleukin (IL)-10 production from LPS-stimulated macrophages in a dose-dependent manner. It is noteworthy that heat inactivation of GAPDH lost its immunomodulatory activity. Correspondingly, NADH significantly inhibited TNF-α and enhanced IL-10 production with elevation of both M1/M2 macrophage markers. These data suggest that extracellular GAPDH induces intermediate M1/M2 macrophages for termination of inflammation, partly through its enzyme activity for generation of NADH.

原文英語
頁(從 - 到)597-608
頁數12
期刊BioFactors
44
發行號6
DOIs
出版狀態已出版 - 01 11 2018

文獻附註

Publisher Copyright:
© 2017 International Union of Biochemistry and Molecular Biology

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