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Regulation of TNF-α-mediated hyperplasia through TNF receptors, TRAFs, and NF-κB in synoviocytes obtained from patients with rheumatoid arthritis

Title
Regulation of TNF-α-mediated hyperplasia through TNF receptors, TRAFs, and NF-κB in synoviocytes obtained from patients with rheumatoid arthritis
Authors
Youn J.Kim H.-Y.Park J.H.Hwang S.-H.Lee S.Y.Cho C.-S.Lee S.K.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2002
Journal Title
Immunology Letters
ISSN
0165-2478JCR Link
Citation
vol. 83, no. 2, pp. 85 - 93
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Although the etiology of rheumatoid arthritis (RA) has not been clearly understood to date, the hyperplasia of the synovial membrane imposed by pro-inflammatory cytokines has been suggested to play a crucial role in the progression of this disease. TNF-α, a potent pro-inflammatory cytokine, was detected at highly enhanced concentrations in the blood and synovial fluids of patients with RA relative to those of patients with osteoarthritis and normal subjects. To evaluate the role of TNF-α in the synovial hyperplasia during the pathogenic state, we investigated cellular outcomes and molecular mechanisms of synoviocytes in response to TNF-α. Following TNF-α treatment, fibroblast-like synoviocytes (FLS) obtained from patients with RA proliferated, unlike the cells from a normal subject that were unaffected. This TNF-α induced proliferation of synoviocytes obtained from RA patients coincided with down-regulation of TNFR1 and up-regulation of TNFR2 and TRAF1-6, as well as NF-κB activation. TNF-α-induced proliferation of synoviocytes was inhibited by transfection with a dominant negative mutant form of I-κBα cDNA (I-κBαdN). Moreover, following TNF-α treatment, transfectants with I-κBαdN underwent apoptosis, whereas mock-transfectants did not. Taken together, these results suggest that high levels of TNF-α present in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis and promoting proliferation of synoviocytes through NF-κB-dependent signaling pathways mediated by up-regulated TNFR2 and TRAF1-6 molecules. © 2002 Elsevier Science B.V. All rights reserved.
DOI
10.1016/S0165-2478(02)00079-2
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자연과학대학 > 생명과학전공 > Journal papers
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