Hyposaline LUSO Mineral Water Drives Murine Macrophage Polarization Towards an Anti‐Inflammatory M2 Phenotype

The beneficial effect of Natural Mineral Water (NMW) in the alleviation and/or treatment of inflammation‐associated diseases has long been empirically recognized, but its scientific validation is still scarce. This study focused on the effect of a Portuguese NMW in modulating the phenotypical characteristics of macrophages, both at homeostasis and in an inflammatory context. As far as we know, we were the first to address the effects of NMW on macrophage polarization. We used RAW 264.7 macrophages cultured in regular medium (control) or LUSO NMW‐containing medium, alone or exposed to lipopolysaccharide (LPS). We explored LUSO NMW effect on macrophage profile (M1, pro‐inflammatory or M2, anti‐inflammatory), release of inflammation mediators, and phagocytic capacity. LUSO NMW‐cultured macrophages acquired an M2 phenotype and showed decreased Il6 gene expression, and IL‐1β, IL‐6 and tumor necrosis factor‐alpha secretion. Moreover, treated cells exhibited enhanced LPS‐induced phagocytosis. In addition, gene expression and protein levels of the antioxidant enzyme Heme Oxygenase 1 were also increased in LUSO NMW‐exposed cells. Overall, these results strongly support the anti‐inflammatory effect of LUSO NMW and suggest that it may also activate antioxidative pathways, which should be deeply explored, including its use as an adjuvant in immune‐ and anti‐inflammatory‐based therapies.