Induction of GTP-cyclohydrolase I mRNA expression by lectin activation and interferon-gamma treatment in human cells associated with the immune response.

The development of tetrahydrobiopterin synthesis during lectin stimulation of resting human T lymphocytes (Kerler et al. [1989] FEBS Lett., 250:622-624), the interferon-gamma induced neopterin production by human monocytes/macrophages (Huber et al. [1984] J. Exp. Med., 160:310-316), and the control of tetrahydrobiopterin synthesis in activated T cells by the synergistic action of interferon-gamma and interleukin 2 (Ziegler et al. [1990] J. Biol. Chem. 265:17026-17030) were previously explained by modulation of the apparent GTP-cyclohydrolase I activation. In this study we demonstrate that increases in GTP-cyclohydrolase I activity which occur after lectin induction and after cytokine treatment correlate with increased steady state mRNA levels specific for this enzyme. The enhancement of interferon-gamma induced enzyme activity in primed T cells by interleukin 2 also corresponds to further increases in mRNA expression. The steady state GTP-cyclohydrolase I mRNA levels in primed T cells, however, do not correlate with the steep decline which follows the culmination of enzyme activity 44 hours after treatment. This indicates that the down-regulation of apparent GTP-cyclohydrolase I activity is caused by posttranslational modification of the protein.