Fig. 6: Lactate regulates the functional polarization of macrophages in vitro.

a M0 macrophages incubated with conditioned medium (CM) derived from si-VCAM-1 PDAC cells or treated with quercetin alone were less spindle-shaped and were rounder in appearance compared with M0 macrophages incubated with conditioned medium derived from si-NC PDAC cells. b–e Compared with M0 macrophages incubated with conditioned medium derived from si-NC PDAC cells, M0 macrophages incubated with conditioned medium derived from si-VCAM-1 PDAC cells or treated with quercetin alone had significantly lower mRNA levels of CD206, CD163, fibronectin, CCL18, CCL22, and IL-10 b, c and showed markedly lower protein levels of CCL18, CCL22, and IL-10 d, e, as determined by qRT-PCR and ELISA assay, respectively. f–h VCAM-1-derived lactate facilitates the M2-like polarization of macrophages in a dose-dependent manner. f Lactate stimulation induced the alternative activated M2 phenotype macrophages as characterized by a morphological change from an epithelial-like, cobblestone phenotype to a more spindle-shaped mesenchymal phenotype. g, h Compared with M0 macrophages incubated with 0 mmol/l lactate, M0 macrophages treated with increasing concentrations (5, 15, 25 mmol/l) of lactate had significantly higher mRNA levels of CD206, CD163, fibronectin, CCL18, CCL22, and IL-10 and showed prominently higher protein levels of CCL18, CCL22 and IL-10, as determined by qRT-PCR and ELISA assay, respectively