Daidzein enhances efferocytosis via transglutaminase 2 and augmentation of Rac1 activity

Jia Hau Yen, Deng Jye Yang, Meng Chi Chen, Wu Yi-Ying, Yu Fan Hsieh, Yueh Mei Cheng, Wen Nan Huang, Zsuzsa Szondy, Gregory J. Tsay*

*此作品的通信作者

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

Clearance of apoptotic cells, termed ". efferocytosis", is the mechanism required to prevent secondary necrosis and release of proinflammatory cytokines. Defective efferocytosis is cumulatively regarded as one of mechanisms in the development of autoimmune and chronic inflammatory diseases. Our previous finding showed that ethanolic extract from Glycine tomentella Hayata (GTH) can enhance mouse macrophage RAW264.7 efferocytosis (clearance of apoptotic cells). We have demonstrated that the major components of GTH are daidzein, catechin, epicatechin and naringin. Here, we explore the potential of each component in modulating efferocytic capability. For this, RAW264.7 cells were cultured with CFDA-stained apoptotic cells and assayed by flow cytometry. We found that daidzein is the main component of GTH, and it can enhance RAW264.7 efferocytosis dose-dependently. Moreover, the enhancive effect of daidzein on macrophage efferocytic capability is accompanied by increased transglutaminase 2 (TG2) at both mRNA and protein levels. TG2 knockdown attenuated daidzein increased macrophage efferocytic capability. After treatment with daidzein, increased phosphorylation was observed in Erk, but not in p38 and JNK. Finally, we report that after daidzein treatment, Rac1 activity was markedly increased and the mitochondrial membrane potential was decreased, which may contribute to efferocytosis. Taken together, these data suggest that enhancement of macrophage efferocytic capability by daidzein treatment was mainly through up-regulation of TG2 expression and Rac1 activity. Daidzein may have the therapeutical potential in the treatment of inflammatory diseases.

原文English
頁(從 - 到)135-142
頁數8
期刊Molecular Immunology
60
發行號2
DOIs
出版狀態Published - 8月 2014

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