Abstract
Serum amyloid A (SAA) is, like C-reactive protein (CRP), an acute phase protein and can be used as a diagnostic, prognostic or therapy follow-up marker for many diseases. Increases in serum levels of SAA are triggered by physical insults to the host, including infection, trauma, inflammatory reactions and cancer. The order of magnitude of increase in SAA levels varies considerably, from a 10- to 100- fold during limited inflammatory events to a 1000-fold increase during severe bacterial infections and acute exacerbations of chronic inflammatory diseases. This broad response range is reflected by SAA gene duplications resulting in a cluster encoding several SAA variants and by multiple biological functions of SAA. SAA variants are single-domain proteins with simple structures and few post-translational modifications. SAA1 and SAA2 are inducible by inflammatory cytokines, whereas SAA4 is constitutively produced. We review here the regulated expression of SAA in normal and transformed cells and compare its serum levels in various disease states. At low concentrations (10-100 ng/ml), early in an inflammatory response, SAA induces chemokines or matrix degrading enzymes via Toll-like receptors and functions as an activator and chemoattractant through a G protein-coupled receptor. When an infectious or inflammatory stimulus persists, the liver continues to produce more SAA (≥ 1000 ng/ml) to become an antimicrobial agent by functioning as a direct opsonin of bacteria or by interference with virus infection of host cells. Thus, SAA regulates innate and adaptive immunity and this information may help to design better drugs to treat specific diseases.
Keywords: SAA variants, FPR2, TLR2, leukocytes, chemotaxis, cytokines, inflammatory diseases, amyloidosis.
Current Medicinal Chemistry
Title:Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Volume: 23 Issue: 17
Author(s): Mieke De Buck, Mieke Gouwy, Ji Ming Wang, Jacques Van Snick, Ghislain Opdenakker, Sofie Struyf and Jo Van Damme
Affiliation:
Keywords: SAA variants, FPR2, TLR2, leukocytes, chemotaxis, cytokines, inflammatory diseases, amyloidosis.
Abstract: Serum amyloid A (SAA) is, like C-reactive protein (CRP), an acute phase protein and can be used as a diagnostic, prognostic or therapy follow-up marker for many diseases. Increases in serum levels of SAA are triggered by physical insults to the host, including infection, trauma, inflammatory reactions and cancer. The order of magnitude of increase in SAA levels varies considerably, from a 10- to 100- fold during limited inflammatory events to a 1000-fold increase during severe bacterial infections and acute exacerbations of chronic inflammatory diseases. This broad response range is reflected by SAA gene duplications resulting in a cluster encoding several SAA variants and by multiple biological functions of SAA. SAA variants are single-domain proteins with simple structures and few post-translational modifications. SAA1 and SAA2 are inducible by inflammatory cytokines, whereas SAA4 is constitutively produced. We review here the regulated expression of SAA in normal and transformed cells and compare its serum levels in various disease states. At low concentrations (10-100 ng/ml), early in an inflammatory response, SAA induces chemokines or matrix degrading enzymes via Toll-like receptors and functions as an activator and chemoattractant through a G protein-coupled receptor. When an infectious or inflammatory stimulus persists, the liver continues to produce more SAA (≥ 1000 ng/ml) to become an antimicrobial agent by functioning as a direct opsonin of bacteria or by interference with virus infection of host cells. Thus, SAA regulates innate and adaptive immunity and this information may help to design better drugs to treat specific diseases.
Export Options
About this article
Cite this article as:
Buck De Mieke, Gouwy Mieke, Wang Ming Ji, Snick Van Jacques, Opdenakker Ghislain, Struyf Sofie and Damme Van Jo, Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults, Current Medicinal Chemistry 2016; 23 (17) . https://dx.doi.org/10.2174/0929867323666160418114600
DOI https://dx.doi.org/10.2174/0929867323666160418114600 |
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
-
Beneficial Effects of N-acetylcysteine and N-mercaptopropionylglycine on Ischemia Reperfusion Injury in the Heart
Current Medicinal Chemistry Pediatric CKD and Cardivascular Disease
Cardiovascular & Hematological Disorders-Drug Targets Chronic Hyperuricemia, Uric Acid Deposit and Cardiovascular Risk
Current Pharmaceutical Design The Role of EC-IC Bypass in Critical Cerebral Hemodynamics of Different Origin
Current Hypertension Reviews Psychological Treatments for Cognitive Dysfunction in Major Depressive Disorder: Current Evidence and Perspectives<sup>§</sup>
CNS & Neurological Disorders - Drug Targets Risk Stratification for Sudden Cardiac Death: Current Approaches and Predictive Value
Current Cardiology Reviews Host Defence Cryptides from Human Apolipoproteins: Applications in Medicinal Chemistry
Current Topics in Medicinal Chemistry Radix Astragali (Astragalus): Latest Advancements and Trends in Chemistry, Analysis, Pharmacology and Pharmacokinetics
Current Organic Chemistry Association of Low Vitamin D with Complications of HIV and AIDS: A literature Review
Infectious Disorders - Drug Targets Targeting Myocardial Metabolism for the Treatment of Stable Angina
Current Pharmaceutical Design Stem Cell Based Tissue Engineering and Regenerative Medicine: A Review Focusing on Adult Stem Cells
Current Tissue Engineering (Discontinued) What Changes we may Expect in 2010 Hypertension Diagnosis and Management: Insights from the European Update Document
Current Vascular Pharmacology Platelet SERT as a Peripheral Biomarker of Serotonergic Neurotransmission in the Central Nervous System
Current Medicinal Chemistry The Role of Infections in the Pathogenesis of Autoimmune Diseases
Current Drug Targets - Inflammation & Allergy Trends in Metabolic Syndrome and Gene Networks in Human and Rodent Models
Endocrine, Metabolic & Immune Disorders - Drug Targets Foreword:
Current Pharmaceutical Design COVID-19: Are Experimental Drugs a Cure or Cause?
Current Drug Safety Synthetic Glucocorticoids: Antenatal Administration and Long-term Implications
Current Pharmaceutical Design The Triad: Erectile Dysfunction - Endothelial Dysfunction - Cardiovascular Disease
Current Pharmaceutical Design Label-Free Cell Phenotypic Drug Discovery
Combinatorial Chemistry & High Throughput Screening