title: Modifications of inflammatory pathways in rat intestine following chronic ingestion of depleted uranium.
abstract: The environmental contamination by dispersion of depleted uranium (DU) might result in its chronic ingestion of DU by local populations. The aim of this study was to determine if chronic ingestion of DU at low doses induces inflammatory reactions in intestine, first biological system exposed to uranium after ingestion. Experiments were performed with rats receiving uranium in drinking water (40 mg/l) during 3, 6, or 9 months. Several parameters referring to prostaglandin, histamine, cytokine, and nitric oxide (NO) pathways were assessed in ileum. Concerning the prostaglandin pathway, a twofold increase in gene expression of cyclooxygenase of type 2 was noted after 6 months, with no changes in prostaglandins levels. At the same time, a decrease in mast cell number was observed without any changes in histamine levels. Experiments on cytokines showed increased gene expression of interleukin (IL)-1beta and IL-10 at 6 months, and decreased messenger RNA level of CCL-2. This change was associated with decreased macrophage density. An opposite effect of DU was induced on neutrophils, since increased number was observed at 3 (x1.7) and 9 months (x3). The results obtained on NO pathway seemed to indicate that DU exposure inhibited this pathway (decreased endothelial NO synthase messenger RNA, inductive NO synthase activity and NO(2)(-)/NO(3)(-) levels) at 6 months. In conclusion, this study demonstrated that chronic ingestion of DU-induced time-dependent modifications of inflammatory pathways, notably in terms of immune cell content. The ultimate effects of DU contamination might be pathogenic by suppressing defense mechanisms or inducing hypersensitivity. Further experiments should be thus performed to determine real consequences on intestinal response to oral antigens.
authors.affiliation: IRSN, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie expérimentale, F-92262 FONTENAY-aux-ROSES CEDEX, France. isabelle.dublineau@irsn.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.forename: Line
authors.initials: L
authors.lastname: Grandcolas
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grison
authors.forename: Cédric
authors.initials: C
authors.lastname: Baudelin
authors.forename: François
authors.initials: F
authors.lastname: Paquet
authors.forename: Philippe
authors.initials: P
authors.lastname: Voisin
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Aigueperse
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014501:Uranium / Q000633:toxicity*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide; D014501:Uranium; D006632:Histamine; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D015232:Dinoprostone