title: Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10.
abstract: Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1β, IL-6, transforming growth factor-β1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Onishi
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Urabe
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirahara
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Muto
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagata
authors.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D015316:Genetic Therapy; D056747:Immunomodulation; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D008297:Male; D056627:Peritoneal Fibrosis / Q000628:therapy*; D010537:Peritoneum / Q000187:drug effects / Q000276:immunology*; D011765:Pyruvaldehyde; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D016753:Interleukin-10; D011765:Pyruvaldehyde