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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.