Bortezomib modulates Toll-like receptor mediated activation of non-parenchymal liver cells and has antiviral activity on HCV replication

Aims: The proteasome inhibitor Bortezomib is used in the treatment of multiple myeloma. Since the proteasome plays a role in TLR-pathways we hypothesized that Bortezomib could also influence TLR mediated activation of non-parenchymal liver cells (NPC) which could be relevant for inflammatory processes in the liver. Methods: Kupffer cells (KC) and LSECs were isolated from CL57/BL mice. Cells were stimulated with TLR3 or TLR4 agonists with or without preincubation with various concentrations of Bortezomib for 1h (7 to 10ng/ml). RNA and nuclear proteins were extracted and analyzed by qt real time PCR and ELISA/West…