title: Gliadin activates arginase pathway in RAW264.7 cells and in human monocytes.
abstract: Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. Recent studies have demonstrated that macrophages play a key role in the pathogenesis of CD through the release of inflammatory mediators such as cytokines and nitric oxide (NO). Since arginine is the obliged substrate of iNOS (inducible nitric oxide synthase), the enzyme that produces large amount of NO, the aim of this work is to investigate arginine metabolic pathways in RAW264.7 murine macrophages after treatment with PT-gliadin (PTG) in the absence and in the presence of IFNγ. Our results demonstrate that, besides strengthening the IFNγ-dependent activation of iNOS, gliadin is also an inducer of arginase, the enzyme that transforms arginine into ornithine and urea. Gliadin treatment increases, indeed, the expression and the activity of arginase, leading to the production of polyamines through the subsequent induction of ornithine decarboxylase. This effect is strengthened by IFNγ. The activation of these pathways takes advantage of the increased availability of arginine due to a decreased system y(+)l-mediated efflux, likely ascribable to a reduced expression of Slc7a6 transporter. A significant induction of arginase expression is also observed in human monocytes from healthy subject upon treatment with gliadin, thus demonstrating that gluten components trigger changes in arginine metabolism in monocyte/macrophage cells.
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. Electronic address: valeria.dallasta@unipr.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Dall'Asta
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005903:Gliadin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009952:Ornithine / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D005903:Gliadin; D001120:Arginine; D009952:Ornithine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D001119:Arginase; D009955:Ornithine Decarboxylase
keywords: Arginase; Arginine; Celiac disease; Gliadin; Interferon-γ; Nitric oxide