Abstract
Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkins lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy.
Keywords: Interferon, interferon receptor, antiviral, immunomodulation, apoptosis, JAK/STAT signaling, clinical applications, cancer
Current Medicinal Chemistry
Title: Interferon: Cellular Executioner or White Knight?
Volume: 14 Issue: 12
Author(s): S. G. Maher, A. L. Romero-Weaver, A. J. Scarzello and A. M. Gamero
Affiliation:
Keywords: Interferon, interferon receptor, antiviral, immunomodulation, apoptosis, JAK/STAT signaling, clinical applications, cancer
Abstract: Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkins lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy.
Export Options
About this article
Cite this article as:
Maher G. S., Romero-Weaver L. A., Scarzello J. A. and Gamero M. A., Interferon: Cellular Executioner or White Knight?, Current Medicinal Chemistry 2007; 14 (12) . https://dx.doi.org/10.2174/092986707780597907
DOI https://dx.doi.org/10.2174/092986707780597907 |
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
-
Nuclear Receptor SHP as a Potential Therapeutic Target for Liver Cancer
Current Cancer Therapy Reviews Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment
Current Cardiology Reviews Current Status and Perspectives in Ceramide-Targeting Molecular Medicine
Current Pharmaceutical Design Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry Salinomycin: A Novel Anti-Cancer Agent with Known Anti-Coccidial Activities
Current Medicinal Chemistry Significance of Prion and Prion-Like Proteins in Cancer Development, Progression and Multi-Drug Resistance
Current Cancer Drug Targets Self-Assembling Peptides: Potential Role in Tumor Targeting
Current Pharmaceutical Biotechnology Antibodies As Promising Novel Neuroprotective Agents in the Central Nervous System Injuries
Central Nervous System Agents in Medicinal Chemistry Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents
Current Medicinal Chemistry Studies on Non-synonymous Polymorphisms Altering Human DNA Topoisomerase II-Alpha Interaction with Amsacrine and Mitoxantrone: An <i>In Silico</i> Approach
Current Cancer Drug Targets A Review of Cationic Arylfurans and Their Isosteres: Synthesis and Biological Importance
Current Organic Chemistry Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Artemisia Species as a New Candidate for Diabetes Therapy: A Comprehensive Review
Current Molecular Medicine Nucleosides with Modified Sugar Ring: Synthesis and Biological Activities
Current Organic Chemistry Role of Chemokines and Their Receptors in Cancer
Current Pharmaceutical Design Population Pharmacogenomics and Personalized Medicine Research in Hungary: Achievements and Lessons Learned
Current Pharmacogenomics and Personalized Medicine Targetin g Human Tel omerase by Antisens e Oligonucleotides and Ribozymes
Current Medicinal Chemistry - Anti-Cancer Agents The Hereditary Disease Array Group (HDAG) - Microarrays, Models and Mechanisms : A Collaboration Update
Current Genomics Failure of Immune Homeostasis - The Consequences of Under and Over Reactivity
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Glycosphingolipid Structure and Function in Membranes
Current Organic Chemistry