Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65

Malcolm L. Handel, Brigham and Women’s Hospital
Linda B. McMorrow, Harvard School of Public Health
Ellen M. Gravallese, University of Massachusetts Medical School

At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.


OBJECTIVE: To identify the cells that express transcription factor NF-kappa B subunits p50 and p65 in synovial tissue from patients with rheumatoid arthritis (RA) and to correlate the distribution of p50 and p65 with CD14 (macrophage lipopolysaccharide receptor) and members of the AP-1 transcription factor family, Jun and Fos.

METHODS: Immunohistochemistry was used to identify p50, p65, Jun and Fos in sections of synovial tissue from 13 patients with RA and 4 "normal" control subjects. Double staining for CD14 and each of the transcription factor subunits was performed.

RESULTS: Subunits p50 and p65 were present in the nuclei of synovial cells in all 13 RA patients, with expression varying from rare cells to more than half of all cells. In most cases, nuclear p50 and p65 were present in approximately one-third of synovial lining cells and in a variable proportion of cells scattered throughout the sublining region, including the endothelium. The distributions of p50 and p65 were similar. Jun and Fos were present in the nuclei of a large proportion of synovial lining cells with significantly less expression elsewhere. In each case the Jun/Fos distribution was clearly different from the p50/p65 distribution, although there was significant overlap in many cases. Cells expressing CD14 were mostly Jun/Fos negative and were predominantly p50/p65 positive. There was negligible staining for p50 or p65 in the 4 normal control synovium samples.

CONCLUSION: In most RA patients, the p50 and p65 subunits of NF-kappa B were present in the majority of CD14-positive cells within the lining and sublining regions and in a proportion of other cells throughout the synovium, including endothelial cells. NF-kappa B is likely to play an important role in the expression of macrophage-derived cytokines in rheumatoid synovium. Different but overlapping distributions of nuclear p50 and p65 versus Jun and Fos indicate separate or divergent mechanisms for the activation of NF-kappa B and the expression of AP-1 proteins in rheumatoid synovium.