Inflammation controls sensitivity of human and mouse intestinal epithelial cells to galectin-1

MUGLIA CECILIA; PAPA GOBBI RODRIGO; SMALDINI PAOLA; ORSINI DELGADO MARIA LUCIA; CANDIA MARTIN; ZANUZZI CAROLINA; SAMBUELLI ALICIA; ROCCA ANDRES; TOSCANO MARTA; RABINOVICH GABRIEL; DOCENA GUILLERMO H.

JOURNAL OF CELLULAR PHYSIOLOGY

wWLEY

Año: 2015

1097-4652

Galectins play key roles in the inflammatory cascade. In this study we aimed to analyze the effect of galectin-1 (Gal-1) in the function of intestinal epithelial cells (IECs) isolated from healthy and inflamed mucosa. IECs isolated from mice or patients with inflammatory bowel diseases (IBD) were incubated with different pro-inflammatory cytokines, and Gal-1 binding, secretion of homeostatic factors and viability were assessed. Experimental models of food allergy and colitis were used to evaluate the in vivo influence of inflammation on Gal-1 binding and modulation of IECs.We found an enhanced binding of Gal-1 to: a) murine IECs exposed to IL-1β, TNF, and IL-13, b) IECs from inflamed areas in intestinal tissue from IBD patients, c) small bowel of allergic mice and d) colon from mice with experimental colitis. Our results showed that low concentrations of Gal-1 favored a tolerogenic microenvironment, while high concentrations of this lectin modulated viability of IECs through mechanisms involving activation of caspase-9- and modulation of Bcl-2 protein family members. Our results showed that, when added in the presence of diverse pro-inflammatory cytokines such as tumor necrosis factor (TNF), IL-13 and IL-5, Gal-1 differentially promoted the secretion of growth factors including thymic stromal lymphopoietin (TSLP), epidermal growth factor (EGF), IL-10, IL-25, and transforming growth factor (TGF)-β1.In conclusion, we found an augmented binding of Gal-1 to IECs when exposed in vitro or in vivo to inflammatory stimuli, showing different effects depending on Gal-1 concentration. These findings highlight the importance of the inflammatory microenvironment of mucosal tissues in modulating IECs susceptibility to the immunoregulatory lectin Gal-1 and its role in epithelial cell homeostasis.