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.

Serum galectins as potential biomarkers of inflammatory bowel diseases

“…The much lower median serum galectin-3 level in healthy people (7.1ng/ml) reported in the Cibor study than in this (22.0ng/ml) and a few other studies [30] indicates that bigger cohorts of patients may be needed in future studies to clarify the discrepancy. It is known that several galectin members including galectin-3 [31] and galectin-1 [32,33] can interact with cell surface glycans and induce endothelium, epithelium or T cell secretion of pro-inflammatory cytokines. For example, galectin-3 interaction with cell surface CD146 (MCAM) on vascular endothelial cells enhances endothelial secretion of IL-6, G-CSF and GM-CSF [34].…”

“…For example, galectin-3 interaction with cell surface CD146 (MCAM) on vascular endothelial cells enhances endothelial secretion of IL-6, G-CSF and GM-CSF [34]. Interaction of galectin-1 with intestinal epithelial cells in the presence of TNFα, IL-13 or IL-5 was shown to enhance epithelial secretion of IL-10, IL-25, and TGF-β1 [32]. The presence of higher concentrations of galectin-1 caused significant increase of Il-10 secretion from CD4(+) and CD8(+) T-cells [33].…”

“…Moreover, an increased circulation of galectins may themselves have an impact on the pathogenesis and progression of IBD. Indeed, galectin-1 interaction with intestinal epithelial cells was altered in the presence of inflammatory stimuli and modulated cell behaviours [32] and inflammation development [36]. Soluble galectin-3 produced by colon epithelial cells was reported to be a strong activator of colonic lamina propria fibroblasts by inducing cell NF-kappaB activation and IL8 secretion [12].…”

Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation

“…Using a multivariate-linear discriminant analysis, a specific galectin signature could be identified that distinguished inflamed IBD from control tissue or from other intestinal inflammatory conditions (114). Inflammatory stimuli controlled Gal-1 binding to epithelial cells, influencing epithelial cell survival and production of tolerogenic cytokines (IL-10, IL-25, and TGF-b 1 ) (115,116). Thus, either through elimination of Ag-experienced T cells or through modulation of inflammatory cytokines, Gal-1 promotes the resolution of gut inflammation, acting as a RAMP in mucosal homeostasis.…”

Galectin-1 inhibits oral-intestinal allergy syndrome

“…It is known that Gal1 has the immune suppression functions [9]. By promoting the secretion of thymic stromal lymphopoietin, epidermal growth factor, IL-10, IL-25, and transforming growth factor-β1 by intestinal epithelial cells, Gal1 can inhibit experimental intestinal inflammation [16]. It induces IL-10 expression in dendritic cells and CD4+ T cells to facilitate the generation of immune regulatory cells [17].…”