Abstract
Bortezomib is the first proteasome inhibitor to be used clinically for the treatment of multiple myeloma and has been suggested as a possible treatment for a wide variety of hematologic and solid malignancies. Recent data suggests that potent immunomodulatory effects can also occur with systemic proteasome inhibition. This has been recently shown to occur in a graft-versus host disease model following bone marrow transplantation in mice. The suggested direct immunological effects of bortezomib treatment to include a decrease in anti-apoptotic protein levels, an increase in expression of TNF-family receptors (specifically Apo2L/TRAIL), induction of apoptosis, and inhibition of the transcription factor NF-κB. The NF-κB pathway has been associated with the regulation of numerous immune and inflammatory response mediators. In this review, we will present recent information concerning the potential therapeutic implications of bortezomib for a range of immune disorders. These findings would suggest that bortezomib treatment may be of clinical significance to suppress solid organ transplant rejection, autoreactive T cell responses, pro-inflammatory cytokine production, and consequently disease progression and pathology in autoimmunty.
Original language | English (US) |
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Pages (from-to) | 29-34 |
Number of pages | 6 |
Journal | Endocrine, Metabolic and Immune Disorders - Drug Targets |
Volume | 7 |
Issue number | 1 |
State | Published - Mar 2007 |
Externally published | Yes |
Keywords
- Autoimmunity
- Autoreactive T cell
- Bortezomib
- Graft versus host disease
- Multiple sclerosis
- Proteasome inhibition
- Transplantation
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Immunology and Allergy