Macrophage repolarization by epigallocatechin-3-gallate via NF-κB and CREB1/HO-1

Epigallocatechin-3-gallate (EGCG) is known for having the highest physiological activity in catechins. However, the molecular mechanism of EGCG regarding macrophage polarization/repolarization remains unclear. This study aimed to reveal whether EGCG can directly induce M2 and lead M1 to M2 repolarization mediated by nuclear factor-κB p65 and cAMP response element binding protein 1 (CREB1)/heme oxygenase-1 (HO-1).

To confirm the function of EGCG on macrophage polarization, RAW264.7 cells were treated with EGCG for 12 h, M1 and M2 markers were evaluated (mRNA and protein level, n = 3). Additionally, to clarify whether EGCG can shift the macrophage polarization from M1 to M2, RAW264.7 cells pretreated with lipopolysaccharide from Porphyromonas gingivalis for 12 h were then exposed to EGCG for 12 h, M1 and M2 markers were analyzed (n = 3). Furthermore, to elucidate the molecular mechanism of these results, the mRNA and protein levels of inflammation regulators such as p65, CREB1, and HO-1 and their phosphorylation were analyzed (n = 3). Significance was assessed using the one-way analysis of variance for comparisons and GraphPad Prism software.

EGCG enhanced the expression of the M2 markers CD206 and CD163 while inhibiting that of the M1 markers iNOS and MMP9. Moreover, EGCG changed the macrophage phenotype from M1 to M2. EGCG was found to suppress p65 phosphorylation; however, it promoted HO-1, resulting in the upregulation of CREB1 phosphorylation.

Our results indicated that EGCG had a great potential in macrophage-mediated immune regulation, leading to the control of excessive tissue damage and promoting tissue repair during inflammation.