Abstract
Background/Objective: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed as “alarmins”. Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα.
Results: We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation. We showed that proTα acts pleiotropically, inducing immunomodulatory effects on immune cell populations. We revealed that the immunoreactive region of proTα is the carboxyterminal decapeptide proTα(100-109) and both molecules stimulate innate immune responses, signaling through Toll-like receptors (TLRs), specifically TLR-4. We reported that proTα and proTα(100-109) bind on the surface of human neutrophils on sites involving TLR-4, and cell activation is complemented by cytoplasmic calcium ion influx. Further, we showed that proTα and proTα(100-109) act as adjuvants upstream of lymphocyte stimulation and, in the presence of antigen, promote the expansion of antigen-reactive effectors. Most recently, we reported that proTα(100-109) may accumulate in experimentally inflamed sites and can serve as a surrogate biomarker in severe bacterial infections, proposing that extracellular release of proTα or proTα(100- 109) alerts the immune system during conditions of danger. Conclusion: We, therefore, suggest that proTα, and likely proTα(100-109), act as alarmins, being important immune mediators as well as biomarkers, and could eventually become targets for new therapeutic/diagnostic approaches in immune-related diseases like cancer, inflammation, and sepsis.Keywords: Prothymosin alpha, proTα(100-109), alarmin, cancer, inflammation, sepsis.
Current Medicinal Chemistry
Title:Prothymosin Alpha: An Alarmin and More...
Volume: 24 Issue: 17
Author(s): Pinelopi Samara, Chrysoula-Evangelia Karachaliou, Kyriaki Ioannou, Nikos E. Papaioannou, Ioannis F. Voutsas, Christos Zikos, Ioannis Pirmettis, Minas Papadopoulos, Hubert Kalbacher, Evangelia Livaniou, Ourania E. Tsitsilonis* Wolfgang Voelter
Affiliation:
- Section of Animal & Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15784,Greece
Keywords: Prothymosin alpha, proTα(100-109), alarmin, cancer, inflammation, sepsis.
Abstract: Background/Objective: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed as “alarmins”. Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα.
Results: We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation. We showed that proTα acts pleiotropically, inducing immunomodulatory effects on immune cell populations. We revealed that the immunoreactive region of proTα is the carboxyterminal decapeptide proTα(100-109) and both molecules stimulate innate immune responses, signaling through Toll-like receptors (TLRs), specifically TLR-4. We reported that proTα and proTα(100-109) bind on the surface of human neutrophils on sites involving TLR-4, and cell activation is complemented by cytoplasmic calcium ion influx. Further, we showed that proTα and proTα(100-109) act as adjuvants upstream of lymphocyte stimulation and, in the presence of antigen, promote the expansion of antigen-reactive effectors. Most recently, we reported that proTα(100-109) may accumulate in experimentally inflamed sites and can serve as a surrogate biomarker in severe bacterial infections, proposing that extracellular release of proTα or proTα(100- 109) alerts the immune system during conditions of danger. Conclusion: We, therefore, suggest that proTα, and likely proTα(100-109), act as alarmins, being important immune mediators as well as biomarkers, and could eventually become targets for new therapeutic/diagnostic approaches in immune-related diseases like cancer, inflammation, and sepsis.Export Options
About this article
Cite this article as:
Samara Pinelopi, Karachaliou Chrysoula-Evangelia , Ioannou Kyriaki, E. Papaioannou Nikos , F. Voutsas Ioannis , Zikos Christos, Pirmettis Ioannis , Papadopoulos Minas, Kalbacher Hubert , Livaniou Evangelia, E. Tsitsilonis Ourania*, Voelter Wolfgang, Prothymosin Alpha: An Alarmin and More..., Current Medicinal Chemistry 2017; 24 (17) . https://dx.doi.org/10.2174/0929867324666170518110033
DOI https://dx.doi.org/10.2174/0929867324666170518110033 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors
Anti-Cancer Agents in Medicinal Chemistry The Discovery of the Potent and Selective Antitumour Agent 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203) and Related Compounds
Current Medicinal Chemistry Protein Misfolding in Conformational Disorders: Rescue of Folding Defects and Chemical Chaperoning
Mini-Reviews in Medicinal Chemistry Herbal Based Polymeric Nanoparticles as a Therapeutic Remedy for Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Polymeric Nanocarriers and Nanoreactors: A Survey of Possible Therapeutic Applications
Current Pharmaceutical Design Oligonucleotide Aptamers for Glioma Targeting: An Update
Central Nervous System Agents in Medicinal Chemistry Anti-breast Cancer Potential of Natural and Synthetic Coumarin Derivatives
Current Topics in Medicinal Chemistry Magnetic Nanoparticles as Both Imaging Probes and Therapeutic Agents
Current Topics in Medicinal Chemistry Cancer Stem Cells in Prostate Cancer Chemoresistance
Current Cancer Drug Targets Fluorinated Molecules as Drugs and Imaging Agents in the CNS
Current Topics in Medicinal Chemistry Cyclin Dependent Kinase 1 Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Emerging Opportunities and Concerns for Drug Discovery at Serotonin 5-5-HT2B Receptors
Current Topics in Medicinal Chemistry Fragment-based Discovery of Potential Anticancer Lead: Computational and in vitro Studies
Current Computer-Aided Drug Design Editorial [Hot Topic: Stem Cells and Tissue Regeneration (Executive Guest Editor: Roberta Di Pietro)]
Current Pharmaceutical Design The Role of Target Therapy in the Treatment of Gastrointestinal Noncolorectal Cancers: Clinical Impact and Cost Consideration
Current Cancer Drug Targets Recent Progress in the Identification and Clinical Evaluation of Inhibitors of the Mitotic Kinesin KSP
Current Topics in Medicinal Chemistry Genistein Inhibits Cell Growth and Invasion Through Regulation of miR-27a in Pancreatic Cancer Cells
Current Pharmaceutical Design A Review of Natural and Synthetic Antioxidants Important for Health and Longevity
Current Medicinal Chemistry Growth and Trophic Factors, pH and the Na+/H+ Exchanger in Alzheimers Disease, Other Neurodegenerative Diseases and Cancer: New Therapeutic Possibilities and Potential Dangers
Current Alzheimer Research Translational Multimodality Neuroimaging
Current Drug Targets