Rheumatoid arthritis and function, gene expression and gene polymorphism of tristetraprolin.

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Tristetraproline (TTP) is an intracellular protein that destabilizes TNFa.mRNA and suppresses TNF α production. We aimed to analyze the role of TTP in rheumatoid arthritis (RA)1. Introduction of the TTP gene into a Human T cell line resulted in reduction of the TNFα mRNA. Response to PHA stimulation was also decreased.2. No significant relationship was observed between the expressions of TTP, TIA-1 or HuR gene, and serum CRP in synovial tissues from patients with RA. However, significant relationship between. gene expressions of TIA-1 and HuR was found.3. Gene expressions of TNFa, TIA-1, TIA-1/HuR were higher and TTP, HuR, TTP/TNFa, TTP/HuR lower in peripheral blood mononuclear cells (PBMC) of RA patients than those from controls. TTP/HuR decreased after introduction of Infliximab. Significant relationships were observed between expression of TIA-1 and TNFα, and TTP and TIA-1 in controls and RA patients after Infliximab treatment. TIA-1/HuR before Infliximab therapy tended to be higher in Infliximab effective patients.4. RA patients with genotype GG of a SNP in the promoter region of the TTP gene tended to have an earlier age of onset than those with AG or AA.They also had a higher probability of having Infliximab introduced.5. TTP transgenic mice tended to be more resistant to collagen induced arthritis than controls.