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Objectives: In this study, we aimed to investigate whether glutathione (GSH) could decrease the secretion of reactive oxygen species (ROS), reduce inflammation, and modulate the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol 3-kinase/AKT (PTEN/PI3K/AKT) in synovial fibroblasts (SFs). Patients and methods: A total of 30 DBA/1J female mice were used in this study. The release of ROS in MH7A cells was examined using a ROS assay kit. The effects of GSH on the messenger ribonucleic acid (mRNA) expression and protein levels of inflammatory cytokines were determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) in mouse SFs and MH7A cells, respectively. The PTEN/PI3K/AKT pathway was investigated via Western blotting. The effects of buthionine-sulfoximine (BSO), as an inhibitor of GSH, on these molecules were examined. Results: The ROS were decreased after GSH treatment, and the mRNA levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)-1, MMP-3, were also significantly inhibited after GSH stimulation. However, the IL-10 levels were enhanced, and GSH increased the expression of PTEN. The GSH suppressed the activation of phosphorylated (p)-PI3K and p-AKT. The supplementation of the BSO restored the activation of PI3K/AKT pathway with a high production of ROS. The levels of TNF-α, IL-1ß and IL-6 were also elevated, when the BSO was added. Conclusion: These findings suggest that GSH can act as an inflammatory suppressor by downregulating the PTEN/PI3K/AKT pathway in MH7A cells. These data indicated a novel function of GSH for improving the inflammation of RA SFs and may help to alleviate the pathological process of RA.
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OBJECTIVES: This study aims to conduct a meta-analysis to clarify the epidemiologic characteristics of biopsy-proven lupus nephritis (BPLN), including those relating to its prevalence and prognosis. PATIENTS AND METHODS: A literature search for relevant studies was conducted in the electronic databases of PubMed, Google Scholar, Embase, and Cochrane trial register. The following search terms were used for original articles published between January 1982 and April 2016: "lupus nephritis" or systemic lupus erythematosus ('SLE') or 'systemic lupus erythematous' and "pathology" or 'epidemiology' or prevalence or incidence. Pooled estimates with 95% confidence intervals were calculated. RESULTS: Nineteen studies were included (mean age of SLE patients at renal biopsy: ~30 years). Of total BPLN patients, 85% were females. BPLN developed in 29% of SLE patients, and accounted for 60% of secondary glomerular diseases in renal biopsy databases. BPLN prevalence among SLE patients was higher in Saudi Arabia compared with pooled Europe/USA data (43% vs 26%, p<0.05). Pooled BPLN prevalence among secondary glomerular diseases patients was higher in Asian/Latin American countries than in Europe (63% vs 34%, p<0.05). Overall five-, 10- and 20-year survival rates of BPLN patients were 94%, 86%, and 71%, respectively, which were higher than those before 1995 (84%, 72%, and 52%, respectively) and lower than those after 1995 (96%, 89%, and 80%, respectively) (all p<0.05). Class IV nephritis, present in 40% of BPLN patients, was a risk factor for renal failure that contributed to poor prognosis. CONCLUSION: Lupus nephritis is a common complication of young female patients with SLE, and the most prevalent etiology of secondary glomerular diseases. Attention should be paid to class IV nephritis due to its high frequency and association with poor prognosis.