title: Sodium chloride-enriched Diet Enhanced Inflammatory Cytokine Production and Exacerbated Experimental Colitis in Mice.
abstract: OBJECTIVE
  Environmental factors are supposed to play a decisive role in the pathogenesis of inflammatory bowel diseases [IBDs]. Increased dietary salt intake has been linked with the development of autoimmune diseases, but the impact of a salt-enriched diet on the course of IBD remains unknown. In this study, we examined whether high salt intake alters mucosal cytokine production and exacerbates colitis.
  
  
  METHODS
  Normal intestinal lamina propria mononuclear cells [LPMCs] were activated with anti-CD3/CD28 in the presence or absence of increasing concentrations of sodium chloride [NaCl] and/or SB202190, a specific inhibitor of p38/MAP Kinase. For in vivo experiments, a high dose of NaCl was administered to mice 15 days before induction of trinitrobenzene-sulfonic acid [TNBS]-colitis or dextran sulfate sodium [DSS]-colitis. In parallel, mice were given SB202190 before induction of TNBS-colitis. Transcription factors and effector cytokines were evaluated by flow-cytometry and real-time PCR.
  
  
  RESULTS
  IL-17A, IL-23R, TNF-α, and Ror-γT were significantly increased in human LPMCs following NaCl exposure, while there was no significant change in IFN-γ, T-bet or Foxp3. Pharmacologic inhibition of p38/MAPK abrogated the NaCl-inducing effect on LPMC-derived cytokines. Mice receiving the high-salt diet developed a more severe colitis than control mice, and this effect was preventable by SB202190.
  
  
  CONCLUSIONS
  Our data indicated that exposure of intestinal mononuclear cells to a high-NaCl diet enhanced effector cytokine production and contributed to the exacerbation of experimental colitis in mice.
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Rome, Italy; ivan.monteleone@uniroma2.it.
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteleone
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Marafini
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dinallo
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Di Fusco
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Troncone
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zorzi
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Laudisi
authors.affiliation: Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D000818:Animals; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D020381:Interleukin-17 / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D018123:Receptors, Interleukin / Q000032:analysis; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D013223:Statistics as Topic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D020381:Interleukin-17; D020011:Protective Agents; D011725:Pyridines; D018123:Receptors, Interleukin; D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha; C528688:interleukin-23 receptor, mouse; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
keywords: Crohn’s disease; Salt; TNF-α; inflammatory bowel diseases; p38; ulcerative colitis