Use of systemic proteasome inhibition as an immune-modulating agent in disease

Lauren H. Mattingly, Ruth A. Gault, William J Murphy

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalEndocrine, Metabolic and Immune Disorders - Drug Targets
Volume7
Issue number1
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Proteasome Endopeptidase Complex
Therapeutics
Apoptosis Regulatory Proteins
Proteasome Inhibitors
Tumor Necrosis Factor Receptors
Immune System Diseases
Graft Rejection
Graft vs Host Disease
Hematologic Neoplasms
Multiple Myeloma
Bone Marrow Transplantation
Disease Progression
Transcription Factors
Apoptosis
Pathology
Cytokines
T-Lymphocytes
Transplants
Bortezomib

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 journalArticle

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