Galectin-1 secreted by bone marrow-derived mesenchymal stem cells mediates anti-inflammatory responses in acute airway disease.

Abstract The hallmarks of allergic airway disease (AAD) include infiltration of inflammatory cells into the bronchoalveolar space. Bone marrow derived mesenchymal stem cells (BMSCs) show anti-inflammatory properties in AAD. In addition, galectin-1 (Gal-1) is a lectin significantly upregulated upon inflammation and is also known to mediate potential anti-inflammatory responses. We hypothesized that BMSCs regulated inflammatory responses by secretion of Gal-1 during AAD pathogenesis. BMSCs were isolated from murine femurs and tibiae and adoptively transferred into an ovalbumin-induced AAD mouse model. Knockdown of Gal-1 in BMSCs was performed using shRNA. Flow cytometry, ELISAs, and immunohistology were performed to analyze inflammatory responses in mice, and a Transwell system was used to establish an in vitro co-culture system of lung epithelial cells (MLE-12) and BMSCs. Administration of BMSCs significantly upregulated Gal-1 expression upon inflammation and decreased infiltration of inflammatory cells and secretion of proinflammatory cytokines in vivo. In addition, we showed that this function was mediated by reduced activation of the MAPK p38 signaling pathway. Similar observations were found using an in vitro lipopolysaccharide-induced model when MLE-12 cells were co-cultured with BMSCs. Gal-1 secretion by BMSCs alleviated inflammatory responses observed in AAD and hence provides a promising therapeutic alternative to AAD patients insensitive to conventional drug treatments.