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Expression of Tristetraprolin (G0S24) mRNA, a Regulator of Tumor Necrosis Factor-a Production, in Synovial Tissues of Patients with Rheumatoid Arthritis
AKITO TSUTSUMI, EIJI SUZUKI, YOSHIHIRO ADACHI, HIDEYUKI MURATA, DAISUKE GOTO, SATOSHI KOJO, ISAO MATSUMOTO, LEI ZHONG, HIROSHI NAKAMURA, and TAKAYUKI SUMIDA
ABSTRACT.
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. (J Rheumatol 2004;31:1044-9) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Division of Rheumatology, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba; and Institute of Clinical Sciences, St. Marianna University, Kawasaki, Japan. A. Tsutsumi, MD, Associate Professor; E. Suzuki, MD, PhD Student; Y. Adachi, MD, Lecturer; H. Murata, MD, Lecturer; S. Kojo, PhD, Laboratory Scientist; I. Matsumoto, MD, Lecturer; D. Goto, MD, Instructor; L. Zhong, MD, Laboratory Scientist; T. Sumida, MD, Professor and Head, Division of Rheumatology, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba; H. Nakamura, MD, Lecturer, Institute of Clinical Sciences, St. Marianna University. Address reprint requests to Dr. A. Tsutsumi, Division of Rheumatology, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. E-mail: atsutsum@md.tsukuba.ac.jp Submitted November 18, 2002; revision accepted December 15, 2003.
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