Objective To determine the expression and regulation of nuclear transcripti
on factors AP-I and NF-kappa B in rheumatoid arthritis and in collagen-indu
ced arthritis in mice.
Methods AP-1 and NF-kappa B expression and function a ere determined in RA,
OA and normal: synovial tissue by electrophoretic mobility shift assay (EM
SA) and immunohistochemistry. The kinetics of transcription factor expressi
on were then examined in collagen-induced arthritis (CIA) in mice. EMSAs a
ere performed with the nuclear extracts obtained from paws of CLA mice from
10 to 45 d after immunization to determine AP-1 and NF-kappa B binding act
ivity. The expression of collagenase-3 (MMP13) and stromelysin (MMP3) mRNA
was examined by northern blot analysis.
Results Immunohistochemistry showed that NF-kappa B expression was increase
d in both RA and OA synovial intimal lining. AP-1 components Jun and Fos we
re also present in the intimal Lining and nas significantly greater in RA t
han OA, The DNA binding activities of both AP-I and NF-kappa B were signifi
cantly higher RA patients compared with OA. In CIA, AP-1 and NF-kappa B exp
ression increased by day 20, which was 1-2 weeks before onset of clinical a
rthritis. However, collagenase and stromelysin gene expression did not incr
ease until day 35,
Conclusion The DNA binding activity of AP-1 and NF-kappa B are markedly inc
reased in both CIA and RA, In CIA, activation of AP-I and NF-kappa B preced
e both clinical arthritis and metalloproteinase gene expression. NF-kappa B
expression correlated better than AP-1 with metalloproteinase expression.