Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-α 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-alpha (TNF-alpha) genes was measured by TaqMan real-time semiquantification PCR. In RA samples, expression of TTP mRNA was compared with TNF-alpha 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-alpha 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-alpha gene expression ratio (p = 0.0071, Spearman rank correlation). Conclusion. A low TTP/TNF-alpha gene expression ratio could indicate failure of RA patients to produce adequate amounts of TTP in response to increased TNF-alpha production. Inappropriate TTP production may be one factor that contributes to higher RA disease activity.