Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-alpha production, in synovial tissues of patients with rheumatoid arthritis.
OBJECTIVE
To determine the significance of tristetraprolin (TTP) gene expression in synovial tissues of patients with rheumatoid arthritis (RA).


METHODS
Gene expression was examined in synovial tissue and peripheral blood lymphocytes of a patient with RA by differential display-polymerase chain reaction (PCR). One of the identified genes, TTP, was selected for further analysis. cDNA was prepared from synovial tissues of 22 patients with RA and 22 with osteoarthritis (OA). Expression of TTP and tumor necrosis factor-a (TNF-a) genes was measured by TaqMan real-time semiquantification PCR. In RA samples, expression of TTP mRNA was compared with TNF-a mRNA, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and steroid and/or disease modifying antirheumatic drug use.


RESULTS
Expression of TTP gene was significantly higher in synovial tissues of RA patients than in OA. There was no apparent relationship between expression of TTP and TNF-a genes. TTP gene expression had a tendency to be inversely correlated with serum CRP, measured immediately before surgery. In addition, CRP was higher in patients with a low TTP/TNF-a gene expression ratio (p = 0.0071, Spearman rank correlation).


CONCLUSIONS
A low TTP/TNF-a gene expression ratio could indicate failure of RA patients to produce adequate amounts of TTP in response to increased TNF-a production. Inappropriate TTP production may be one factor that contributes to higher RA disease activity.
Tsutsumi
Akito
A
Division of Rheumatology, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. atsutsum@md.tsukuba.ac.jp
Suzuki
Eiji
E
Adachi
Yoshihiro
Y
Murata
Hideyuki
H
Goto
Daisuke
D
Kojo
Satoshi
S
Matsumoto
Isao
I
Zhong
Lei
L
Nakamura
Hiroshi
H
Sumida
Takayuki
T
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D004268:DNA-Binding Proteins; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D012217:Rheumatoid Factor / Q000097:blood; D013583:Synovial Membrane / Q000502:physiology*; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; C497552:ZFP36 protein, human; D002097:C-Reactive Protein; D012217:Rheumatoid Factor