Ganoderma atrum polysaccharide modulates the M1/M2 polarization of macrophages linked to the Notch signaling pathway

Macrophages could be polarized into two major sub-populations including classically activated (M1) and alternatively activated (M2) macrophages. The present study aimed to investigate the effects of Ganoderma atrum polysaccharide (PSG-1) on the regulation of macrophage polarization and further explored the associated molecular mechanisms. In this work, a lipopolysaccharide (LPS) plus IFN-gamma and IL-4 were used to establish an in vitro model of two extreme states, namely pro-inflammatory M1 and anti-inflammatory M2. The results showed that PSG-1 had effects on the behavior modification of macrophage polarization by reducing CD80 expression in LPS plus IFN-gamma-induced M1 macrophages, and attenuating CD23 expression in IL-4-induced M2 macrophages. Further study revealed that PSG-1-modulated M1 and M2 macrophage polarization was associated with controlling phagocytosis, reactive oxygen species generation, NO and cytokines (IL-1 beta, IL-6 and IL-10). Subsequently, the treatment of M1 macrophages with a combination of PSG-1 and a Notch-response inhibitor (DAPT) did not alter CD80 expression compared with DAPT alone, while several pro-inflammatory parameters were considerably decreased, suggesting that the Notch signaling pathway partly mediated the effects of PSG-1 on modulating macrophage polarization. Together, our findings suggested that PSG-1 could repair the chaos in the polarization of M1/M2 macrophages and the molecular mechanism linked to the Notch signaling pathway.