Expression of Tristetraprolin (G0S24) mRNA, a Regulator of TNF-a Production, in Synovial Tissues of Patients with RA

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J Rheumatol. 2004 Jun;31(6):1044-9.

Expression of Tristetraprolin (G0S24) mRNA, a Regulator of Tumor

Necrosis Factor-a Production, in Synovial Tissues of Patients with

Rheumatoid Arthritis.

Tsutsumi A, Suzuki E, Adachi Y, Murata H, Goto D, Kojo S, Matsumoto I,

Zhong L, Nakamura H, Sumida T.

Division of Rheumatology, Department of Internal Medicine, Institute of

Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

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).

CONCLUSION: 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.

PMID: 15170914

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