Suzuki Eiji, Tsutsumi Akito, Sugihara Makoto, Mamura Mizuko, Goto Daisuke, Matsumoto Isao, Ito Satoshi, Ikeda Kotaro, Ochiai Naoyuki, Sato Yukio, Sumida Takayuki
Department of Clinical Immunology, University of Tsukuba, Ibaraki 305-8575, Japan.
Int J Mol Med. 2006 Aug;18(2):273-8.
Post-transcriptional regulation through the AU-rich element (ARE) by ARE binding proteins (ARBPs) has an important role in controlling the production of cytokines, including tumor necrosis factor (TNF)-alpha. Therefore, expression of ARBPs may influence, or may be influenced, by the severity of rheumatoid arthritis (RA). We measured the gene expression of ARBPs, including tristetraprolin, T-cell intracellular antigen (TIA)-1 and Hu antigen R (HuR), in synovial tissues from RA and osteoarthritis patients. cDNA was constructed from synovial tissues obtained from 21 patients with RA, and those from 12 patients with osteoarthritis. Gene expression was measured using the TaqMan PCR real-time quantification method. No significant differences were observed in the expression of tristetraprolin, TIA-1 or HuR genes between RA and osteo-arthritis synovium samples. No significant relationships between expression of tristetraprolin, TIA-1 or HuR genes and TNF-alpha gene expression serum CRP levels in samples from RA patients were observed. A significant positive relationship was observed between gene expression levels of TIA-1 and HuR. While HuR stabilizes TNF-alpha mRNA and enhances TNF-alpha production, TIA-1 acts as a post-transcriptional silencer, and suppresses the production of the TNF-alpha protein. The clear positive relationship between the expression of these two ARBPs may imply that the expression of either gene affects the expression of the other, or the mechanisms that control the expression of these genes have some factors in common.
富含AU元件(ARE)结合蛋白(ARBP)介导的转录后调控在控制包括肿瘤坏死因子(TNF)-α在内的细胞因子产生中发挥重要作用。因此,ARBP的表达可能会受到类风湿关节炎(RA)严重程度的影响,或者反之影响RA的严重程度。我们检测了RA患者和骨关节炎患者滑膜组织中包括锌指蛋白36、T细胞内抗原(TIA)-1和Hu抗原R(HuR)在内的ARBP的基因表达。从21例RA患者和12例骨关节炎患者获取的滑膜组织构建cDNA。使用TaqMan PCR实时定量方法检测基因表达。在RA和骨关节炎滑膜样本之间,锌指蛋白36、TIA-1或HuR基因的表达未观察到显著差异。在RA患者样本中,未观察到锌指蛋白36、TIA-1或HuR基因表达与TNF-α基因表达及血清CRP水平之间存在显著相关性。观察到TIA-1和HuR的基因表达水平之间存在显著正相关。虽然HuR可稳定TNF-α mRNA并增强TNF-α的产生,但TIA-1作为转录后沉默子,可抑制TNF-α蛋白的产生。这两种ARBP表达之间明显的正相关可能意味着任一基因的表达会影响另一个基因的表达,或者控制这些基因表达的机制有一些共同因素。