Serum amyloid A, the major vertebrate acute-phase reactant.
The serum amyloid A (SAA) family comprises a number of differentially expressed apolipoproteins, acute-phase SAAs (A-SAAs) and constitutive SAAs (C-SAAs). A-SAAs are major acute-phase reactants, the in vivo concentrations of which increase by as much as 1000-fold during inflammation. A-SAA mRNAs or proteins have been identified in all vertebrates investigated to date and are highly conserved. In contrast, C-SAAs are induced minimally, if at all, during the acute-phase response and have only been found in human and mouse. Although the liver is the primary site of synthesis of both A-SAA and C-SAA, extrahepatic production has been reported for most family members in most of the mammalian species studied. In vitro, the dramatic induction of A-SAA mRNA in response to pro-inflammatory stimuli is due largely to the synergistic effects of cytokine signaling pathways, principally those of the interleukin-1 and interleukin-6 type cytokines. This induction can be enhanced by glucocorticoids. Studies of the A-SAA promoters in several mammalian species have identified a range of transcription factors that are variously involved in defining both cytokine responsiveness and cell specificity. These include NF-kappaB, C/EBP, YY1, AP-2, SAF and Sp1. A-SAA is also post-transcriptionally regulated. Although the precise role of A-SAA in host defense during inflammation has not been defined, many potential clinically important functions have been proposed for individual SAA family members. These include involvement in lipid metabolism/transport, induction of extracellular-matrix-degrading enzymes, and chemotactic recruitment of inflammatory cells to sites of inflammation. A-SAA is potentially involved in the pathogenesis of several chronic inflammatory diseases: it is the precursor of the amyloid A protein deposited in amyloid A amyloidosis, and it has also been implicated in the pathogenesis of atheroscelerosis and rheumatoid arthritis.
Uhlar
C M
CM
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA.
Whitehead
A S
AS
D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology*; D000686:Amyloidosis / Q000209:etiology; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000276:immunology*; D001161:Arteriosclerosis / Q000209:etiology; D001172:Arthritis, Rheumatoid / Q000209:etiology; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014158:Transcription, Genetic
D000209:Acute-Phase Proteins; D001053:Apolipoproteins; D016207:Cytokines; D005938:Glucocorticoids; D000685:Serum Amyloid A Protein