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• W2046874504 abstract "<i>Objective:</i> Due to the crucial role of the glucocorticoid receptor (GR), nuclear factor ĸB (NFĸB), activator protein-1 (AP-1) and c-jun N-terminal kinase (JNK) in regulating inflammatory mediators and immune responses, we investigated their potential role in systemic lupus erythematosus (SLE). <i>Patients and Methods:</i> Whole cell and nuclear extracts from peripheral blood lymphocytes, isolated from 25 SLE patients and 25 controls, were immunoblotted using GR, p65/NFĸB, c-fos and JNK1 antibodies. The electrophoretic mobility shift assay (EMSA) assessed GR, NFĸB and AP-1-DNA binding in nuclear aliquots. Associations with the disease state and the doses of corticosteroids administered were studied. <i>Results:</i> (i) SLE patients had lower GR-DNA binding (p < 0.001), NFĸB-DNA binding (p < 0.001) and whole cell c-fos (p < 0.01) but higher nuclear NFĸB (p < 0.01). (ii) SLE patients and controls had similar AP-1-DNA binding, nuclear c-fos, GR and JNK, whole cell GR, NFĸB and JNK. (iii) No differences were detected between active and non-active SLE or high- and low-dose corticosteroid patients. (iv) In SLE, increases in GR-DNA binding were associated with increases in NFĸB-DNA binding (p < 0.0001), and increases in nuclear JNK were associated with increases in AP-1-DNA binding (p < 0.01). (v) In controls, increases in GR-DNA binding were associated with increases in AP-1-DNA binding (p < 0.001). <i>Conclusion:</i> We suggest disturbed GR, NFĸB, AP-1 and JNK signaling in SLE, characterized by a reduced GR- and NFĸB-DNA binding, a significant association between GR-mediated and NFĸB-driven pathways, and a significant correlation between nuclear JNK- and AP-1-driven pathways. These disturbances may contribute to abnormal cytokine production and the etiopathogenesis of SLE." @default.
• W2046874504 created "2016-06-24" @default.
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• W2046874504 date "2006-01-01" @default.
• W2046874504 modified "2023-09-27" @default.
• W2046874504 title "Glucocorticoid Receptor, Nuclear Factor κB, Activator Protein-1 and C-Jun N-Terminal Kinase in Systemic Lupus Erythematosus Patients" @default.
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• W2046874504 doi "https://doi.org/10.1159/000100474" @default.
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