Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas                 expression, serum soluble Fas and disease activity

Courtney, P A; Crockard, A.D.; Williamson, Kate E.; McConnell, Jeff; Kennedy, Rebekah; Bell, A. L.

doi:10.1191/096120399678840765

Cited by 60 publications

(53 citation statements)

References 35 publications

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“…We therefore used fluorocytometry to investigate the surface expression of class I MHC molecules (HLA-A/B/C), of HLA-DR, and of CD95 as well as their possible association with STAT-1 expression. As expected (4,7,45,46), comparing SLE lymphocytes with those from healthy individuals, we observed increased expression of class I MHC and HLA-DR (MFI 554 Ϯ 139 versus 403 Ϯ 118 [P ϭ 0.001] and 9.0 Ϯ 3.8 versus 6.8 Ϯ 1.9 [P Ͻ 0.01], respectively). Similarly, the MFI of CD95 on SLE lymphocytes was significantly increased compared with that on lymphocytes from healthy individuals (11.4 Ϯ 4.1 versus 8.7 Ϯ 2.2; P Ͻ 0.01).…”

Section: Correlation Of Stat-1 Levels With Expression Of Other Ifn-insupporting

confidence: 82%

Activation of the interferon‐γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells

Karonitsch¹,

Feierl²,

Steiner³

et al. 2009

Arthritis & Rheumatism

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Conclusion. In addition to supporting the role of IFNs in SLE immunopathogenesis in general, the findings of the present study support a role of IFN␥ in this disease.Type I interferons (e.g., IFN␣) and type II IFN (IFN␥) have both been implicated in the immunopathogenesis of systemic lupus erythematosus (SLE). IFN␣ and IFN␥ serum levels are increased (1-5), and IFN messenger RNA (mRNA) signatures are expressed in the peripheral blood cells of SLE patients (6-8). IFN␣ and IFN␥ are known to induce SLE flares and druginduced lupus (9-11). In murine models of the disease, both IFN␣ and IFN␥ may be pathogenetically important (12-15), and, especially, a deficiency in either IFN␥ or the IFN␥ receptor (IFN␥R) totally abates the disease process (16)(17)(18)(19).IFNs act on a variety of cells, including lymphocytes and monocytes (20,21). The biologic effects of IFN␣ and IFN␥ are mediated via the phosphorylation, and thus the activation, of members of the STAT family

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Section: Correlation Of Stat-1 Levels With Expression Of Other Ifn-insupporting

confidence: 82%

Activation of the interferon‐γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells

Karonitsch¹,

Feierl²,

Steiner³

et al. 2009

Arthritis & Rheumatism

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“…23 The enhanced serum levels of soluble Fas demonstrated that the intriguing effect of the Fas/FasL pathway on cell death was related to disease activity. [24][25][26] These findings indicate that in SLE patients, the Fas/ FasL pathway plays an important role in immune homeostasis and maintenance of self-tolerance. However, gene mutation in the coding regions of FasL rarely occurs in human lupus patients.…”

Section: Introductionmentioning

confidence: 87%

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Chen¹,

Wang²,

Chi³

et al. 2005

Genes Immun

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FasL expression is critical in T-cell activation-induced apoptosis, which is involved in lupus pathogenesis. This study identified two SNPs in the FasL promoter regions from -1145 to -45 by genomic DNA sequencing. The -844C/T polymorphism was previously described by its location in and affect on the CCAAT/enhancer-binding protein b (C/EBPB b)-binding site and the other (-1094A/C, a novel polymorphism) was located at the NF-kB transcription-binding site. FasL gene promoter polymorphisms were genotyped in 260 systemic lupus erythematosus (SLE) patients and 280 healthy controls using MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. The distribution of FasL promoter -844C/C genotype, predominant in Taiwanese, was skewed in Taiwanese SLE patients (odds ratio: 1.53; P-value ¼ 0.014). FasL promoter À844C/T polymorphism genotype distributions of Taiwanese, African Americans, and Caucasians differed. Moreover, no particular clinical association of À844C/T and À1094A/C polymorphisms with SLE was found in patients in Taiwan. This study confirmed that À844C/C genotype is associated with lupus susceptibility. The -1094A/C polymorphism is not significantly associated with lupus disease susceptibility, albeit the role of NF-kB pathway in FasL promoter activation remains unclear. Fas/FasL pathway may contribute to SLE polygenic disease entity.

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“…[8][9][10] Lymphocyte Fas expression and serum soluble Fas were significantly increased in systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease patients. 11 The expression of Fas may be tightly regulated by a number of factors. Several proteins were identified to regulate Fas expression, such as TDAG51, 12 nuclear factor-kB 13 and cyclon.…”

Section: Introductionmentioning

confidence: 99%

Let-7/miR-98 regulate Fas and Fas-mediated apoptosis

Tang

Cui

et al. 2011

Genes Immun

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Fas is ubiquitously expressed on a variety of cells and triggers apoptosis, which have critical roles in the immune system. MicroRNAs (miRNAs) have been recently identified as regulators that modulate target gene expression and are involved in diverse biological processes, such as cell proliferation and apoptosis. This study was undertaken to investigate the contribution of miRNA in the regulation of Fas expression and Fas-mediated apoptosis. Bioinformatics analysis indicated that Fas was a potential target of let-7/miR-98 family. Indeed ectopic expression of let-7/miR-98 reduced, whereas knockdown of endogenous let-7/miR-98 increased the expression of Fas at both mRNA and protein levels. Let-7/miR-98 was verified to target Fas 3 0 untranslated region directly by site-directed gene mutagenesis and reporter gene assay. More importantly, introduction of let-7/miR-98 could decrease the sensitivity to Fas-induced apoptosis. Furthermore, let-7/miR-98 expression was reduced in activation-induced cell death process, accompanied by increased expression of Fas. In conclusion, our study first demonstrated that let-7/miR-98 regulated Fas expression and the sensitivity of Fas-mediated apoptosis.

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Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas expression, serum soluble Fas and disease activity

Cited by 60 publications

References 35 publications

Activation of the interferon‐γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells

Activation of the interferon‐γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells

The −844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE

Let-7/miR-98 regulate Fas and Fas-mediated apoptosis

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