Abstract:
:Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects various organs and systems. Increased apoptosis, together with defects in the uptake of apoptotic bodies, are thought to have a pathogenic role in SLE. By detection of chromatin condensation, 30% of apoptosis was detected in peripheral blood mononuclear cells (PBMC) from Thai patients with active SLE. Therefore, understanding of the molecular processes in PBMC apoptosis may allow us to gain insight into pathophysiology of SLE. Thus, genes involved in the apoptosis of PBMC from these patients were investigated ex vivo by cDNA array analysis. Seventeen apoptosis-related genes were stimulated in active SLE, more than twofold higher than in inactive SLE. These genes are classified into six groups, namely death receptors, death ligands, caspases, bcl-family, and neutral proteases and genes involved in endoplasmic reticulum stress-mediated apoptosis, such as caspase-4 and GADD153. Among those stimulated genes, tumor necrosis factor (TNF) and the TNF-receptor family were drastically up-regulated 60- and 19-fold higher than in healthy controls, respectively. Moreover, the degree of apoptosis correlated with the level of TNF-alpha in plasma, suggesting that the TNF family plays a role in the induction of apoptosis in SLE. To verify this hypothesis, PBMC from healthy individuals were treated with plasma from active SLE patients in the presence or absence of etanercept, a TNF inhibitor. In the presence of etanercept, active SLE plasma reduced the level of apoptosis to 26.43%. In conclusion, massive apoptotic death of PBMC occurred during the active stage of SLE. The molecular pathway of SLE-PBMC apoptosis was mediated at least via TNF/TNFR signaling pathway, which was confirmed by functional test of TNF-alpha in SLE patients' plasma.
journal_name
Clin Rheumatoljournal_title
Clinical rheumatologyauthors
Pitidhammabhorn D,Kantachuvesiri S,Totemchokchyakarn K,Kitiyanant Y,Ubol Sdoi
10.1007/s10067-005-0162-5subject
Has Abstractpub_date
2006-09-01 00:00:00pages
705-14issue
5eissn
0770-3198issn
1434-9949journal_volume
25pub_type
杂志文章abstract::Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organs/systems with variable activities. We performed a retrospective study to investigate the relationship of clinical characteristics and complications with SLE activity in Chinese Han population. A cohort of 1,490 SLE inpatients w...
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doi:10.1007/s10067-009-1097-z
更新日期:2009-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/BF02242999
更新日期:1994-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s10067-009-1186-z
更新日期:2010-01-01 00:00:00
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更新日期:2003-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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