Dataset Information

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.

SUBMITTER: Kim HR

PROVIDER: S-EPMC3990669 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function.

Kim Hyung-Ran HR Lee Anbok A Choi Eun-Jeong EJ Kie Jeong-Hae JH Lim Woosung W Lee Hyeon Kook HK Moon Byung-In BI Seoh Ju-Young JY

PloS one 20140417 4

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 ...[more]

PMID: 24743300

Similar Datasets

Project description:PurposeThe antioxidant enzymes pathway is considered the most important pathway involved in the repair of reactive oxygen species (ROS)-induced damage. Therefore, we investigate the possible association between polymorphisms of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPX) genes and age -related cataract development.MethodsThe study included 415 cataract patients (121 patients with cortical, 109 with nuclear, 59 with posterior subcapsular, and 126 with mixed type) and 386 healthy control group of similar age. Genotyping of SOD1-251A/G, CAT-21A/T, and GPX1-198C/T was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated using the χ(2) test and risk was estimated with an unconditional logistic regression after adjusting for age and gender.ResultsSOD1 G/G genotype frequency was significantly higher in cataract patients (p=0.012, OR=1.642, 95% CI=1.129-2.389). SOD1 A/A genotypes (p=0.001, OR=0.613, 95% CI=0.461-0.817) seem to have a protective role against cataract, and the G allele (p=0.001, OR=1.479, 95% CI=1.208-1.810) plays a dangeous effect against in the development of cataract. In CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls (p=0.226, OR=1.358, 95% CI=0.839-2.199; p=0.521, OR=1.205, 95% CI=0.726-2.001, respectively). Stratification by the subtypes revealed that association between SOD polymorphism and cataract was in cortical and mixed type cataract. The genotype frequency of the GG and AA of SOD1-251A/G was significantly different in cortical and mixed type cataract group (p=0.031; OR: 1.805, 95% CI: 1.076-3.026; p=0.002; OR: 2.229, 95% CI: 1.364-3.645; p=0.026; OR: 0.608, 95% CI: 0.396-0.933; p=0.001; OR: 0.474, 95% CI: 0.305-0.734, respectively) compared to healthy controls.ConclusionsResults suggest that the G/G genotype of the SOD1-251A/G polymorphism may be associated with an increased risk of cataract. However, in CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls.

Dataset Information

Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function.

Publications

Attenuation of experimental colitis in glutathione peroxidase 1 and catalase double knockout mice through enhancing regulatory T cell function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets