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) |
|---|---|
| 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 |
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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
Cite this
Use of systemic proteasome inhibition as an immune-modulating agent in disease. / Mattingly, Lauren H.; Gault, Ruth A.; Murphy, William J.
In: Endocrine, Metabolic and Immune Disorders - Drug Targets, Vol. 7, No. 1, 03.2007, p. 29-34.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Use of systemic proteasome inhibition as an immune-modulating agent in disease
AU - Mattingly, Lauren H.
AU - Gault, Ruth A.
AU - Murphy, William J
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Autoreactive T cell
KW - Bortezomib
KW - Graft versus host disease
KW - Multiple sclerosis
KW - Proteasome inhibition
KW - Transplantation
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M3 - Article
C2 - 17346202
AN - SCOPUS:33847735872
VL - 7
SP - 29
EP - 34
JO - Endocrine, Metabolic and Immune Disorders - Drug Targets
JF - Endocrine, Metabolic and Immune Disorders - Drug Targets
SN - 1871-5303
IS - 1
ER -