Increased synovial tissue NF-kappa B1 expression in RA

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Arthritis Rheum. 2004 Jun;50(6):1781-7.

Increased synovial tissue NF-kappa B1 expression at sites adjacent to

the cartilage-pannus junction in rheumatoid arthritis.

Benito MJ, E, EP, van den Berg WB, FitzGerald O, Bresnihan

B.

St. 's University Hospital, Elm Park, Dublin, Ireland.

OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits,

NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples

selected from sites adjacent to and remote from the cartilage-pannus

junction (CPJ) in patients with inflammatory arthritis. METHODS:

Synovial tissue was selected at arthroscopy from sites adjacent to the

CPJ and from the suprapatellar pouch of patients who were referred to an

early arthritis clinic. Tissue samples from patients with osteoarthritis

(OA) undergoing knee arthroplasty were also studied. Rel/NF-kappa B

subunit activation and expression were measured by electrophoretic

mobility shift assay and supershift analyses and by

immunohistochemistry. RESULTS: Tissue samples were obtained from 10

patients with rheumatoid arthritis (RA), 7 with a seronegative

arthropathy (SnA), and 6 with OA. Rel/NF-kappa B was abundantly

expressed in all samples. In both RA and SnA synovial tissue, the

absolute number of NF-kappa B1+ cells at the CPJ was significantly

higher than at non-CPJ sites (P = 0.006 and P = 0.02, respectively). The

proportion of cells expressing NF-kappa B1 was also significantly higher

at the CPJ compared with non-CPJ sites (P = 0.003 in RA, P = 0.009 in

SnA). The numbers of RelA+ cells were consistently lower throughout. In

RA synovial tissue, but not in SnA synovial tissue, both the absolute

number and the proportion of RelA+ cells were significantly higher at

the CPJ than at non-CPJ sites (P = 0.003 and P = 0.01, respectively). In

OA synovial tissue, the numbers of cells expressing NF-kappa B1 and RelA

were similar to those observed at the non-CPJ sites in all inflammatory

tissues studied.

CONCLUSION: In this study of early inflammatory arthritis, expression of

NF-kappa B1 in synovial tissue was highest at sites most likely to be

associated with joint erosion. These observations are consistent with a

critical role of NF-kappa B1 in joint destruction, and support the

rationale for specific therapeutic inhibition of NF-kappa B in RA.

PMID: 15188354

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