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|標題:||Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-18 in patients with active untreated adult-onset Still's Disease||作者:||Chen, D.Y.
|關鍵字:||apoptosis;interleukin-18;apoptosis-regulating genes;adult-onset;still's disease;systemic lupus erythematosus;systemic-lupus-erythematosus;flow-cytometric detection;programmed;cell-death;in-vitro apoptosis;fas ligand;phosphatidylserine;expression;lymphoproliferative syndrome;pathological tissues;autoimmune-diseases;interferon-gamma||Project:||Arthritis & Rheumatism-Arthritis Care & Research||期刊/報告no：:||Arthritis & Rheumatism-Arthritis Care & Research, Volume 57, Issue 8, Page(s) 1530-1538.||摘要:||
Objective. To determine spontaneous and activation-induced apoptosis of peripheral blood lymphocytes (PBLs) from patients with active untreated adult-onset Still's disease (AOSD) and to examine the role of interleukin-18 (IL-18) involved in the apoptosis related to this disease. Methods. The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes in peripheral blood of 20 patients with active untreated AOSD, 20 with active untreated systemic lupus erythematosus (SLE), and 20 healthy controls were determined using annexin V/propidium iodide staining and flow cytometry. Serum IL-18 levels were measured using enzyme-linked immunosorbent assay. The transcripts of caspase 3 gene and apoptosis-regulating genes, including Fas, FasL, Bcl-2, and p53 in IL-18-treated peripheral blood mononuclear cells (PBMCs) from 8 AOSD patients, 4 SLE patients, and 4 healthy controls, were examined by real-time quantitative polymerase chain reaction. Results. Significantly higher percentages of spontaneous and IL-18-stimulated apoptotic PBLs were found in patients with active untreated AOSD and those with active untreated SLE than in healthy controls. The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes correlated positively with clinical activity scores and serum IL-18 levels for AOSD patients and SLE patients. The percentages of spontaneous and activation-induced apoptotic PBLs significantly declined, paralleling clinical remission and the decrease in serum IL-18 levels after effective therapy in AOSD patients. Up-regulation of FasL, and p53 transcripts was demonstrated in IL-18-treated PBMCs from AOSD patients and SLE patients in a dose-dependent manner. Conclusion. The increased apoptosis of PBLs from AOSD patients may be associated with the effect of IL-18 through up-regulation of FasL and p53 transcripts.
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