INFLAMMATION CONTROLS SENSITIVITY OF HUMAN AND MOUSE EPITHELIAL CELLS TO GALECTIN-1

MUGLIA CECILIA; PAPA GOBBI RODRIGO; SMALDINI, PAOLA; ORSINI DELGADO L; CANDIA MARTÍN; ZANUCCI, CAROLINA

Journal of cellular physiology

Wiley Periodicals

Año: 2015

1097-4652

Galectins are involved at different stages of inflammatory disorders. Galectin-1 (Gal-1), mostly described for its anti-inflammatory properties, could exert a modulatory effect on intestinal epithelial cells (IEC) death, thus affecting barrier integrity and gut permeability. This study aims to analyze the pro-apoptotic effect of Gal-1 on intestinal epithelial cells in healthy and inflamed contexts of mouse and human mucosa.Intestinal epithelial cells were isolated from gut of BALB/C mice and human colon explants. Cells were cultured with different pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-5 and IL-13) and Gal-1 binding was analyzed by flow cytometry. Apoptosis was assessed by annexin V and JC1 by flow cytometry, and TUNEL by confocal microscopy. Bcl family proteins and caspasases were also evaluated. In addition, food allergy and colitis mouse models were employed to evaluate how in vivo experimental inflammation influences intestinal epithelial cells to undergo apoptosis upon incubation with Gal-1. Moreover, colonic biopsies of IBD and control patients were cultured with Gal-1, and further assessed for lectin binding and cell apoptosis.We found that Gal-1 binding and Gal-1-induced apoptosis was significantly enhanced when IEC were incubated with Gal-1 in the presence of IL-1β, TNF-α, or IL-13. In all cases, the mitochondrial pathway was involved. IEC isolated from inflamed small bowel of mice sensitized with cholera toxin plus allergen, or from inflamed colon of mice with TNBS-induced colitis showed a significant increase in Gal-1 binding and subsequent cell apoptosis upon exposure to Gal-1. Similar results were observed in biological specimens from inflamed areas of IBD patients.In conclusion, our results provide evidence of the pro-apoptotic role of Gal-1 on IEC in pro-inflammatory microenvironments, which may impact on integrity of the gut barrier and propagate the mucosal inflammation.