Abstract
Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA). Among PDE4 inhibitors, apremilast, roflumilast, and crisabolore have been approved for the treatment of psoriasis and PsA, chronic obstructive pulmonary disease, and atopic dermatitis, respectively. In a preliminary study on psoriasis and PsA we showed that at 6 months apremilast decreased IFNγ+CD3+ Th1 cells and IL- 17+CD3+ Th17 cells and increased regulatory B cells and regulatory T cells. In this review, we highlight recent findings of PDE4 inhibitors in atopic dermatitis, alopecia areata, uveitis, rheumatoid arthritis, psoriasis and PsA, systemic lupus erythematosus, vasculitis, systemic sclerosis, multiple sclerosis and inflammatory bowel disease. Given the role of cAMP as second messenger in diverse intracellular pathways, selective PDE4 inhibitors are likely to be therapeutic agents for various immune mediated diseases.
Keywords: Apremilast, autoimmunity, bregs, cAMP, tregs, psoriatic arthritis, psoriasis.
Current Medicinal Chemistry
Title:Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives
Volume: 24 Issue: 28
Author(s): Lazaros I. Sakkas*, Athanasios Mavropoulos and Dimitrios P. Bogdanos
Affiliation:
- Department of Rheumatology and clinical Immunology Faculty of Medicine, School of Health Science University of Thessaly, Larissa 41 110,Greece
Keywords: Apremilast, autoimmunity, bregs, cAMP, tregs, psoriatic arthritis, psoriasis.
Abstract: Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA). Among PDE4 inhibitors, apremilast, roflumilast, and crisabolore have been approved for the treatment of psoriasis and PsA, chronic obstructive pulmonary disease, and atopic dermatitis, respectively. In a preliminary study on psoriasis and PsA we showed that at 6 months apremilast decreased IFNγ+CD3+ Th1 cells and IL- 17+CD3+ Th17 cells and increased regulatory B cells and regulatory T cells. In this review, we highlight recent findings of PDE4 inhibitors in atopic dermatitis, alopecia areata, uveitis, rheumatoid arthritis, psoriasis and PsA, systemic lupus erythematosus, vasculitis, systemic sclerosis, multiple sclerosis and inflammatory bowel disease. Given the role of cAMP as second messenger in diverse intracellular pathways, selective PDE4 inhibitors are likely to be therapeutic agents for various immune mediated diseases.
Export Options
About this article
Cite this article as:
Sakkas I. Lazaros*, Mavropoulos Athanasios and Bogdanos P. Dimitrios , Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives, Current Medicinal Chemistry 2017; 24 (28) . https://dx.doi.org/10.2174/0929867324666170530093902
DOI https://dx.doi.org/10.2174/0929867324666170530093902 |
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
-
Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy
Current Medicinal Chemistry Management of Connective Tissue Interstitial Lung Disease
Current Respiratory Medicine Reviews Update on Intravenous Immunoglobulins (IVIg) Mechanisms of Action and Off- Label use in Autoimmune Diseases
Current Pharmaceutical Design Excess Exposure to Insulin Is the Primary Cause of Insulin Resistance and its Associated Atherosclerosis
Current Molecular Pharmacology MDMA Administration and Heat Shock Proteins Response: Foreseeing a Molecular Link
Current Pharmaceutical Biotechnology Pharmacogenetics and Statin Treatment: Reality or Theory?
Current Vascular Pharmacology Insulin-Degrading Enzyme: Structure-Function Relationship and its Possible Roles in Health and Disease
Current Pharmaceutical Design Biomarkers Determining Cardiovascular Risk in Patients with Kidney Disease
Current Medicinal Chemistry Use of Recombinant Human Erythropoietin as an Antianemic and Performance Enhancing Drug
Current Pharmaceutical Biotechnology Increased Pulmonary Heme Oxygenase-1 and δ-Aminolevulinate Synthase Expression in Monocrotaline-Induced Pulmonary Hypertension
Current Neurovascular Research Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Current Pharmaceutical Design Cocaine and Acute Vascular Diseases
Current Drug Abuse Reviews A Murine Model of Vasculitis Induced by Fungal Polysaccharide
Cardiovascular & Hematological Agents in Medicinal Chemistry Adverse Reactions Induced by Minocycline: A Review of Literature
Current Drug Safety Clinical Characteristics of Behcet’s Disease in 453 Egyptian Patients Suffering from Uveitis with Gender Comparison
Current Rheumatology Reviews Alcohol and the Cardiovascular System: A Double-Edged Sword
Current Pharmaceutical Design Prospective of Natural Gum Nanoparticulate Against Cardiovascular Disorders
Current Chemical Biology Retracted: Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design
Current Pharmaceutical Design The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis
Current Pharmaceutical Design The Role of C-Reactive Protein in Atherosclerotic Cardiovascular Disease: An Overview
Current Vascular Pharmacology