title: Gliadin-mediated production of polyamines by RAW264.7 macrophages modulates intestinal epithelial permeability in vitro.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, SBiBiT, Università degli Studi di Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Barilli
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, SBiBiT, Università degli Studi di Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Rotoli
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, SBiBiT, Università degli Studi di Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Visigalli
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, SBiBiT, Università degli Studi di Parma, Via Volturno 39, 43125 Parma, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ingoglia
authors.affiliation: Dipartimento di Scienze degli Alimenti, Università degli Studi di Parma, Parco Area delle Scienze 49/A, 43124 Parma, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Cirlini
authors.affiliation: Dipartimento di Scienze degli Alimenti, Università degli Studi di Parma, Parco Area delle Scienze 49/A, 43124 Parma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Prandi
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, SBiBiT, Università degli Studi di Parma, Via Volturno 39, 43125 Parma, Italy. Electronic address: valeria.dallasta@unipr.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Dall'Asta
keywords: Arginase; Celiac disease; Gliadin; Intestinal permeability; Polyamines