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Table 2 Overview of effects of proteasome inhibitors on immune cell function

From: Proteasome inhibitors as experimental therapeutics of autoimmune diseases

  Macrophages T cells B cells (plasma cells) Dendritic cells Osteoclasts
MG-132 ↓ activation + pro-inflammatory cytokine production Not documented Not documented Not documented ↓ RANKL-induced osteoclast differentiation and function
↑ anti-inflammatory cytokine production
Bortezomib ↑ ABCA1 and ABCG1 expression ↑ induction of apoptosis in activated and proliferating cells ↓ plasma cells and autoantibody levels in lupus model ↓ CD40, CD86, CD80, HLA-DR, CD206 and CD209 CD83 expression ↓ osteoclasto-genesis and differentiation
Depletion of alloreactive T cells and ↓ Th1 cytokines   ↑ apoptosis by ↑ bax ↑ osteoclasto-genesis and bone destruction
↓ release of NF-κB-inducible cytokines by activated T cells from RA patients   ↓ TLR and Rel A and B activation  
↓ activation, proliferation, survival and important immune functions of human CD4+ T cells   ↓ T-cell stimulation capacity  
↓ TLR trafficking, IFN-α and IL-6
Carfilzomib (PR-171) Not documented Not documented ↓ plasma cells lupus model ↓ TLR trafficking, IFN-α and IL-6 Not documented
↑ apoptosis induction
Delanzomib (CEP-18770/ cephalon) Not documented Not documented ↓ plasma cells and autoantibody levels in lupus model Not documented Not documented
ONX0914 (PR-957) ↓ IL-23 release ↓ IFN-γ and IL-2 ↓ plasma cells and autoantibody levels in arthritis model ↓ TLR trafficking, IFN-α and IL-6 Not documented
Shift from IL-17 to Tregs ↑ apoptosis
↓ DC differentiation and maturation
  1. ABCG1/A1, ATP-binding cassette G1/A1; DC, dendritic cell; IFN, interferon; IL, interleukin; NF-kB, nuclear factor kappa beta; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor-kB ligand; TLR, Toll-like receptor; Treg, regulatory T cell.