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Daidzein enhances efferocytosis via transglutaminase 2 and augmentation of Rac1 activity.

Abstract
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.
AuthorsJia-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
JournalMolecular immunology (Mol Immunol) Vol. 60 Issue 2 Pg. 135-42 (Aug 2014) ISSN: 1872-9142 [Electronic] England
PMID24859791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Isoflavones
  • daidzein
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • rac1 GTP-Binding Protein
Topics
  • Animals
  • Cell Line
  • GTP-Binding Proteins (metabolism)
  • Humans
  • Isoflavones (pharmacology)
  • MAP Kinase Signaling System (drug effects)
  • Membrane Potential, Mitochondrial (drug effects)
  • Mice
  • Phagocytosis (drug effects)
  • Phosphorylation (drug effects)
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases (metabolism)
  • Up-Regulation (drug effects)
  • rac1 GTP-Binding Protein (metabolism)

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