title: Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function.
abstract: Reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases including inflammatory bowel diseases (IBD). Meanwhile, several studies suggested the protective role of ROS in immune-mediated inflammatory diseases, and it was recently reported that dextran sodium sulfate (DSS)-induced colitis was attenuated in mice with an elevated level of ROS due to deficiency of peroxiredoxin II. Regulatory T cells (Tregs) are critical in the prevention of IBD and Treg function was reported to be closely associated with ROS level, but it has been investigated only in lowered levels of ROS so far. In the present study, in order to clarify the relationship between ROS level and Treg function, and their role in the pathogenesis of IBD, we investigated mice with an elevated level of ROS due to deficiency of both glutathione peroxidase (GPx)-1 and catalase (Cat) for the susceptibility of DSS-induced colitis in association with Treg function. The results showed that DSS-induced colitis was attenuated and Tregs were hyperfunctional in GPx1-/- × Cat-/- mice. In vivo administration of N-acetylcysteine (NAC) aggravated DSS-induced colitis and decreased Treg function to the level comparable to WT mice. Attenuated Th17 cell differentiation from naïve CD4+ cells as well as impaired production of IL-6 and IL-17A by splenocytes upon stimulation suggested anti-inflammatory tendency of GPx1-/- × Cat-/- mice. Suppression of Stat3 activation in association with enhancement of indoleamine 2,3-dioxygenase and FoxP3 expression might be involved in the immunosuppressive mechanism of GPx1-/- × Cat-/- mice. Taken together, it is implied that ROS level is critical in the regulation of Treg function, and IBD may be attenuated in appropriately elevated levels of ROS.
authors.affiliation: Department of Microbiology, Ewha Womans University Graduate School of Medicine, Seoul, Korea.
authors.forename: Hyung-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Pathology, National Health Insurance Cooperation Ilsan Hospital, Koyang, Korea.
authors.forename: Anbok
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Ewha Womans University Graduate School of Medicine, Seoul, Korea.
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Department of Surgery, Ewha Womans University Graduate School of Medicine, Seoul, Korea.
authors.forename: Jeong-Hae
authors.initials: JH
authors.lastname: Kie
authors.affiliation: Department of Pathology, National Health Insurance Cooperation Ilsan Hospital, Koyang, Korea.
authors.forename: Woosung
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Pathology, National Health Insurance Cooperation Ilsan Hospital, Koyang, Korea.
authors.forename: Hyeon Kook
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Pathology, National Health Insurance Cooperation Ilsan Hospital, Koyang, Korea.
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Moon
authors.affiliation: Department of Microbiology, Ewha Womans University Graduate School of Medicine, Seoul, Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D016264:Dextran Sulfate; D002374:Catalase; D005979:Glutathione Peroxidase; D000111:Acetylcysteine; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
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