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 Scopus citations

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

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

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