Dialyzable Leukocyte Extract (Dle) Suppresses Transcription Factor Nf-Kb
Activity In Unstimulated Mt-4 Cells
Authors: Ojeda, M., Fernández-Ortega, C. And M.J. Araña
Institution: Cell Biology Division, Center For Biological Research, La
Habana, Cuba.
Abstract:
Dialyzable Leukocyte Extract (DLE) derived from immune lymphocytes is capable
of transferring specific immunity to naive T-cells. Clinical effectiveness
of this biological extract has been demonstrated in a broad spectrum of
diseases. Others have used DLE in AIDS patients and we observed a remarkable
response in asymptomatic Human Immunodeficiency Virus (HIV)-infected individuals
treated with DLE. Among the cellular transcription factors, NF-Kb plays
a key role in the control of transcription of HIV, through the interaction
with specific element from the long terminal repeat (LTR). In this work
we examined the effect of DLE on NF-kB activation by EMSA, in cells that
are commonly used to study HIV replication. The T-lymphocyte cell line
MT-4 was exposed to several doses of DLE (0, 1,25 and 2,5 U/mL) during
seven days, and nuclear extracts were prepared after 0, 3h, 3 and 7 days
of treatment. Under these experimental conditions, we observed a remarkable
inhibitory effect on NF-kB activity by DLE treatment. Reduction of DNA-protein
complex formation was directly related with increments in DLE dose. Surprisingly,
DLE at 2,5 U/mL completely suppressed NF-kB activation after seven days
of MT-$ treatment. This effect is time related with the inhibition of HIV
replication observed after DLE treatment in the same system, as we previously
report. NF-kB is critical for proper immune function, cell growth and survival.
Control of transcription by NF-kB represents a potential regulatory step
of HIV gene expression. Our data indicate that DLE has the remarkable ability
of inhibiting NF-kB DNA-binding activity. These results significantly contribute
to our knowledge of the mechanisms responsible for the effectiveness of
DLE therapy in asymptomatic HIV patients.