Enhanced expression and DNA binding activity of two CCAAT/enhancer-binding protein isoforms, C/EBPbeta and C/EBPdelta, in rheumatoid synovium.
OBJECTIVE
To investigate the activation and expression of CCAAT/enhancer-binding proteins (C/EBP), especially C/EBPbeta and -delta, in rheumatoid synovium, and their pathogenic implications in rheumatoid arthritis (RA).


METHODS
The activation of C/EBPbeta and -delta was assessed in synovial tissues from patients with RA by electrophoretic mobility shift assay (EMSA); DNA binding activity of C/EBPs was evaluated by measuring EMSA band density. The expression and distribution of C/EBPbeta and -delta in synovial tissues were examined by immunohistochemistry analysis. As a control, synovial tissues from patients with osteoarthritis (OA) were studied.


RESULTS
Enhanced DNA binding activity of C/EBPbeta and -delta, 2 major members of the C/EBP family, was detected in synovial tissues from RA patients, while synovial tissues from the patients with OA showed only faint or marginal activity (mean +/- SEM arbitrary units [AU] RA 23.3 +/- 11.7 in RA versus 4.5 +/- 1.3 in OA; P < 0.05). Moreover, the binding activities of the C/EBP proteins were correlated with both serum C-reactive protein levels (r = 0.62, P < 0.05) and synovial interleukin-6 messenger RNA levels (r = 0.60, P < 0.05). In immunohistochemistry studies, C/EBPbeta and -delta were detected predominantly in the rheumatoid synovial lining cells (both CD14+ and CD14- cells).


CONCLUSIONS
C/EBPbeta and -delta may contribute to the pathology of rheumatoid synovitis.
Nishioka
K
K
Osaka University Medical School, Suita City, Japan.
Ohshima
S
S
Umeshita-Sasai
M
M
Yamaguchi
N
N
Mima
T
T
Nomura
S
S
Murata
N
N
Shimizu
M
M
Miyake
T
T
Yoshizaki
K
K
Suemura
M
M
Kishimoto
T
T
Saeki
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004551:Elbow Joint / Q000473:pathology; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007719:Knee Joint / Q000473:pathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D004247:DNA