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.