Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue

Marok, R., Winyard, P. G., Coumbe, A., Kus, M. L., Gaffney, K. ORCID:, Blades, S., Mapp, P. I., Morris, C. J., Blake, D. R., Kaltschmidt, C. and Baeuerle, P. A. (1996) Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue. Arthritis and Rheumatism, 39 (4). pp. 583-591. ISSN 0004-3591

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OBJECTIVE: The transcription factor nuclear factor kappaB (NF-kappaB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF-kappaB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis. METHODS: Immunohistochemical staining was performed using both polyclonal and monoclonal "activity-specific" antibodies to the Rel-A (p65) subunit of NF-kappaB (anti-Rel-A nuclear location sequences). Histologic features of inflammation were also scored. RESULTS: Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining. CONCLUSION: The activation of NF-kappaB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.

Item Type: Article
Uncontrolled Keywords: aged,aged, 80 and over,antibodies, monoclonal,metabolism,chemistry,female,humans,immunohistochemistry,male,middle aged,analysis,metabolism,chemistry
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 26 Aug 2020 00:02
Last Modified: 22 Oct 2022 06:40
DOI: 10.1002/art.1780390407

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