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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.
Clinical Immunology and Immunopathology
|December 1, 1993
Summary
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.