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Daidzein enhances efferocytosis via transglutaminase 2 and augmentation of Rac1 activity (639.10)
Author(s) -
Yen JiaHau,
Chen HsiaoLing,
Tsay Gregory
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.639.10
Subject(s) - efferocytosis , daidzein , pharmacology , apoptosis , syk , chemistry , inflammation , naringin , genistein , macrophage , medicine , endocrinology , immunology , biochemistry , in vitro , signal transduction , tyrosine kinase , chromatography
Objective: Defective efferocytosis is cumulatively recognized in autoimmune and chronic inflammatory diseases. Based on our previous finding, an ethanolic extract from Glycine tomentella Hayata (GTH) can enhance mouse macrophage Raw264.7 efferocytosis (clearance of apoptotic cells). We have previously demonstrated that the major components of GTH are daidzein, catechin, epicatechin and naringin. Here, we explore the potential of each component for modulating efferocytosis activity. Methods and results: For detecting the effect of daidzein, catechin, epicatechin and naringin on efferocytosis, 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 increased effect of daidzein on macrophage efferocytosis activity is accompanied by TG2 at both the mRNA and protein levels. Conversely, TG2 knockdown attenuated the effect of daidzein on increased macrophage efferocytosis activity. After treatment with daidzein, increased phosphorylation was observed in Erk, but not P38 and JNK. Finally, we report that after daidzein treatment, Raw264.7 macrophages markedly increased Rac1 activity and decreased the mitochondrial membrane potential, which may contribute to efferocytosis. Conclusion: Taken together, these data suggest that daidzein enhancement of macrophage efferocytosis activity was mainly through up‐regulation of TG2 expression and Rac1 activity. Daidzein may have the potential for treatment strategies for inflammatory diseases. Grant Funding Source : Supported by NSC 99‐2811‐B‐040‐005, Taiwan