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Inhibition of Itk Adrenorphin by proteasome inhibitors
Fig. 3.
Proteasome inhibitors suppress Itk expression in PBMC. PBMC were treated overnight with MG132 (A) or Bortezomib (B). (C) PBMC were left untreated or stimulated with PHA (2.5 μg/ml) and IL-2 (75 U/ml). Cells were then cultured overnight in the presence of MG132. (?Cells were treated with MG132 for 1 h prior to the addition of PHA and IL-2). (D) PBMC were stimulated with PHA and IL-2 for 3 days, and then infected with HIV-1BaL in the presence of MG132 for 16 h. Relative amount of Itk and p65 levels is demonstrated at the bottom.
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Proteasome inhibitors block HIV-1 replication
The above results show that proteasome inhibitors repress transcriptional activity of the HIV-1 LTR-promoter. To further assess whether these agents affect viral replication, PHA-activated PBMC from healthy individuals were infected with HIV-1BaL in the presence of proteasome inhibitors or the anti-HIV drugs Indinavir (IND) and azidothymidine (AZT). The in vitro concentrations of drugs used here (IND, AZT, and Bortezomib) are comparable to plasma levels in patients receiving therapy [17].





 
 
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