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.
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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 |
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