title: Inflammation Controls Sensitivity of Human and Mouse Intestinal Epithelial Cells to Galectin-1.
abstract: 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 micro-environment, whereas 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 micro-environment of mucosal tissues in modulating IECs susceptibility to the immunoregulatory lectin Gal-1 and its role in epithelial cell homeostasis.
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: Cecilia I
authors.initials: CI
authors.lastname: Muglia
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: Rodrigo Papa
authors.initials: RP
authors.lastname: Gobbi
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: Paola
authors.initials: P
authors.lastname: Smaldini
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: María Lucía Orsini
authors.initials: ML
authors.lastname: Delgado
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: Martín
authors.initials: M
authors.lastname: Candia
authors.affiliation: Departamento de Histología y Embriología, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Zanuzzi
authors.affiliation: Servicio de Enfermedades Inflamatorias, Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sambuelli
authors.affiliation: Servicio de Enfermedades Inflamatorias, Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
authors.forename: Andrés
authors.initials: A
authors.lastname: Rocca
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Toscano
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.|Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata y Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata, Argentina.
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Docena
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000235:genetics; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005512:Food Hypersensitivity / Q000235:genetics / Q000378:metabolism; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D051379:Mice
chemical_list: D037483:Galectin 1