Abstract
P-glycoprotein, the human MDR1 gene product and cancer multidrug resistance-associated ATP-binding cassette transporter, is physiologically expressed on peripheral blood mononuclear cells, but its role in cellular immunity is only beginning to be elucidated. A role of P-glycoprotein in the secretion of several T cell- and antigen presenting cellderived cytokines has been described, and additional functions of the molecule have been identified in lymphocyte survival and antigen presenting cell differentiation. Taken together, these findings provide compelling evidence that Pglycoprotein serves several distinct functions in the initiation of primary immune responses, and a critical role of the molecule in functional immune responses is now established. Here, we will review the current understanding of Pglycoprotein function in T cell activation and antigen presenting cell function, which are relevant to the fields of clinical transplantation and autoimmunity, and summarize the evidence for in vitro and in vivo immunomodulatory actions of several known P-glycoprotein-inhibiting agents currently in clinical use for other indications. We suggest that it is the Pglycoprotein- inhibitory function of many of these agents that underly their immunoregulatory capacities. Thus, the established immunoregulatory function of P-glycoprotein and the availability of P-glycoprotein-inhibitory drugs raise the possibility that P-glycoprotein may represent a promising novel therapeutic target for immune modulation in acute and chronic allograft rejection, and cell-mediated autoimmune disorders.
Keywords: p-glycoprotein, t cells, dendritic cells, natural killer cells, immunosuppression, psc833, tamoxifen, alloimmunity
Current Drug Targets
Title: P-glycoprotein - A Novel Therapeutic Target for Immunomodulation in Clinical Transplantation and Autoimmunity?
Volume: 4 Issue: 6
Author(s): S. Pendse, H. M. Sayegh and H. M. Frank
Affiliation:
Keywords: p-glycoprotein, t cells, dendritic cells, natural killer cells, immunosuppression, psc833, tamoxifen, alloimmunity
Abstract: P-glycoprotein, the human MDR1 gene product and cancer multidrug resistance-associated ATP-binding cassette transporter, is physiologically expressed on peripheral blood mononuclear cells, but its role in cellular immunity is only beginning to be elucidated. A role of P-glycoprotein in the secretion of several T cell- and antigen presenting cellderived cytokines has been described, and additional functions of the molecule have been identified in lymphocyte survival and antigen presenting cell differentiation. Taken together, these findings provide compelling evidence that Pglycoprotein serves several distinct functions in the initiation of primary immune responses, and a critical role of the molecule in functional immune responses is now established. Here, we will review the current understanding of Pglycoprotein function in T cell activation and antigen presenting cell function, which are relevant to the fields of clinical transplantation and autoimmunity, and summarize the evidence for in vitro and in vivo immunomodulatory actions of several known P-glycoprotein-inhibiting agents currently in clinical use for other indications. We suggest that it is the Pglycoprotein- inhibitory function of many of these agents that underly their immunoregulatory capacities. Thus, the established immunoregulatory function of P-glycoprotein and the availability of P-glycoprotein-inhibitory drugs raise the possibility that P-glycoprotein may represent a promising novel therapeutic target for immune modulation in acute and chronic allograft rejection, and cell-mediated autoimmune disorders.
Export Options
About this article
Cite this article as:
Pendse S., Sayegh M. H. and Frank M. H., P-glycoprotein - A Novel Therapeutic Target for Immunomodulation in Clinical Transplantation and Autoimmunity?, Current Drug Targets 2003; 4 (6) . https://dx.doi.org/10.2174/1389450033490894
DOI https://dx.doi.org/10.2174/1389450033490894 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Dietary Polyphenols for Treatment of Alzheimer’s Disease– Future Research and Development
Current Pharmaceutical Biotechnology Compounds Derived from Epigallocatechin-3-Gallate (EGCG) as a Novel Approach to the Prevention of Viral Infections
Inflammation & Allergy - Drug Targets (Discontinued) Role of Nitrosative Stress and Activation of Poly(ADP-ribose) Polymerase-1 in Cardiovascular Failure Associated with Septic and Hemorrhagic Shock
Current Vascular Pharmacology Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways
Current Cancer Drug Targets P2RY12 Increased Neuroinflammation to Accelerate Depression-like Behaviors by the NLPR3 Inflammasome
Current Neurovascular Research Effective Anticancer Drug and Food Choices Based on Polyamine Levels in Cancer Tissues
Current Drug Therapy Thromboxane A2 Receptor Blockade Prevents Atherosclerotic Process by its Anti-Inflammatory Effect
Vascular Disease Prevention (Discontinued) Effect of Aging On Angiogenesis and Arteriogenesis
Current Cardiology Reviews Recent Advances in the Identification of Genetic and Biochemical Components of Breast Cancer Predisposition
Current Genomics Osteoarthritis - Current Insights in Pathogenesis, Diagnosis and Treatment
Current Rheumatology Reviews Recent Patents Relating to Tumor Suppressor Genes
Recent Patents on DNA & Gene Sequences Statins in Bacteremia, Sepsis and Pneumonia: Have We Found the Holy Grail?
Recent Patents on Inflammation & Allergy Drug Discovery Administration of Ethanolic Extract of Ocimum Basilicum Leaves Attenuates Depression like Behavior in the Rats Sensitized by Ovalbumin
Current Nutrition & Food Science Unfolding the Pathophysiological Role of Bioactive Lysophospholipids
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Ultrasound Contrast Agents: Updated Data on Safety Profile
Current Pharmaceutical Design Preface
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Interleukin-17A in Alzheimer’s Disease: Recent Advances and Controversies
Current Neuropharmacology Botulinum Toxin: Pharmacology and Clinical Developments: A Literature Review
Medicinal Chemistry A Walk in Nature: Sesquiterpene Lactones as Multi-Target Agents Involved in Inflammatory Pathways
Current Medicinal Chemistry Angiotensin Converting Enzyme Inhibitor in Coronary Artery Bypass Surgery
Drug Design Reviews - Online (Discontinued)