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The effect of rapamycin on c-jun expression in human lymphocytes
1Laboratory of Nephrology and Transplantation Immunology, Notre-Dame Hospital Research Center, Montreal, Quebec, Canada.
Abstract:
Rapamycin (RAPA) is a potent immunosuppressant. Several reports indicate that the drug can act at the late G1 stage of the lymphocyte activation. We studied the effect of RAPA on the expression of an immediate early phase gene c-jun, which plays a pivotal role in cell activation. The results showed that RAPA could inhibit PHA-induced c-jun expression by human T cells. This strongly suggests that there exists a mechanism for RAPA to interact with the lymphocyte activation cascade at a very early stage. We also demonstrated that in T cells a Na+/K+ ATPase inhibitor, ouabain, could induce a late (16 h poststimulation) c-jun expression, which was sensitive to cyclosporin A (CsA) but not to RAPA. This suggests that c-jun's role is probably not restricted to the early phase of lymphocyte activation.
Insights
Rapamycin (RAPA) inhibits early T cell activation by blocking c-jun gene expression. However, c-jun
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- Rapamycin (RAPA) is a known immunosuppressant drug.
- Previous studies suggest RAPA affects lymphocyte activation late in the G1 phase.
Purpose of the Study:
- To investigate the effect of RAPA on the expression of the immediate early gene c-jun in human T cells.
- To explore the role of c-jun in lymphocyte activation cascades.
Main Methods:
- Human T cells were stimulated with PHA.
- The expression of c-jun was measured following RAPA treatment.
- Ouabain, a Na+/K+ ATPase inhibitor, was used to induce late c-jun expression.
- Sensitivity of induced c-jun expression to RAPA and cyclosporin A (CsA) was assessed.
Main Results:
- RAPA significantly inhibited PHA-induced c-jun expression in human T cells.
- Ouabain induced a late c-jun expression (16 hours post-stimulation).
- Late c-jun expression induced by ouabain was sensitive to CsA but not RAPA.
Conclusions:
- RAPA interacts with the lymphocyte activation cascade at a very early stage by inhibiting c-jun expression.
- The role of c-jun in lymphocyte activation extends beyond the early phase, as evidenced by CsA-sensitive, RAPA-insensitive late expression.