Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro

• Published in: Biochimica et biophysica acta Vol. 1852; no. 9; pp. 1779 - 1786
• Main Authors: Barilli, Amelia, Rotoli, Bianca Maria, Visigalli, Rossana, Ingoglia, Filippo, Cirlini, Martina, Prandi, Barbara, Dall'Asta, Valeria
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2015
• Subjects: Arginase; Celiac disease; Gliadin; Intestinal permeability; Polyamines; Celiac disease; Arginase; Polyamines; Gliadin; Intestinal permeability
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2015.06.001

Celiac disease (CD) is an immune-mediated enteropathy sustained by dietary gluten in susceptible individuals, and characterized by a complex interplay between adaptive and innate responses against gluten peptides (PTG). In a recent contribution we have demonstrated that the treatment with PTG induces the expression and activity of arginase in both murine macrophages and human monocytes from healthy subjects, thus suggesting a role for arginine and its metabolites in gluten-triggered response of these cells. Here we further explore this field, by addressing the effects of PTG on polyamine synthesis and release in murine RAW264.7 macrophages, and how they affect epithelial permeability of Caco-2 monolayers. Results obtained show a massive production and release of putrescine by macrophages upon incubation with gluten peptides; this, in turn, causes a decrease in TEER in epithelial cells, indicating that PTG-driven secretion of polyamines by macrophages has a role in the modulation of intestinal permeability in vitro. At a molecular level, putrescine production appears referable to the activation of C/EBPβ transcription factor, which is known to be responsible for arginase induction in activated macrophages and is a crucial mediator of inflammation. Whether these pathways are stimulated also in vivo deserves to be further investigated, as well as their role in gluten-driven cellular and intestinal defects typical of CD patients. •Gliadin stimulates the production of polyamines in RAW264.7 macrophages.•Polyamines secreted by macrophages affect epithelial permeability.•DFMO and Arg free medium prevent the putrescine-mediated decrease in TEER.•C/EBPβ has a role in arginase induction by PTG in macrophages.•4F2hc/SLC3A2 has a role in the PTG-driven release of putrescine in macrophages.