These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.
The differential use of anatomic and reversed shoulder prostheses in secondary fracture treatment leads to an improvement in postoperative results. In fracture sequelae types 1 and 2, the anatomic prosthesis is a better choice. However, in fracture sequelae types 3 and 4 with severe deformities, the reversed prosthesis is clearly superior to the anatomic prosthesis.
Objective
To investigate the expression of the transcription factor Ets‐1 in synovial tissue and cultured synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the regulation of Ets‐1 expression and activation in synovial fibroblasts by proinflammatory cytokines.
Methods
In situ expression of Ets‐1 in synovial tissue from RA and OA patients was examined by double immunohistochemistry. The effects of interleukin‐1 (IL‐1) or tumor necrosis factor α (TNFα) on Ets‐1 expression and activation (DNA binding) in cultured synovial fibroblasts were analyzed by Western blotting and DNA gel shift assay, respectively. In addition, the intracellular location of Ets‐1 in synovial fibroblasts was determined by immunofluorescence.
Results
Pronounced expression of Ets‐1 was detected in synovial tissues from all RA patients evaluated, particularly in the synovial lining layer and the sublining areas. Ets‐1 was expressed by both fibroblasts and macrophages as well as by endothelial cells, while only a few T cells stained positive for Ets‐1. In synovial specimens from OA patients, Ets‐1 expression was much less frequently observed and was largely restricted to vascular cells. Ets‐1 was expressed to a similar degree in cultured synovial fibroblasts from RA and OA patients, as demonstrated by reverse transcriptase–polymerase chain reaction and Western blotting. Both IL‐1 and TNFα induced pronounced up‐regulation of Ets‐1 in synovial fibroblasts. Moreover, binding of Ets‐1 to its specific DNA binding site was induced by both cytokines, although with different time courses. Immunofluorescence staining revealed a dominant nuclear localization of Ets‐1 in IL‐1– or TNFα‐stimulated synovial fibroblasts.
Conclusion
The overexpression of Ets‐1 observed in RA synovial tissue appears to be caused by TNFα and IL‐1, suggesting that Ets‐1 may be an important factor in the cytokine‐mediated inflammatory and destructive cascade characteristic of RA.
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