title: Emerging functions of serum amyloid A in inflammation.
abstract: SAA is a major acute-phase protein produced in large quantity during APR. The rise of SAA concentration in blood circulation during APR has been a clinical marker for active inflammation. In the past decade, research has been conducted to determine whether SAA plays an active role during inflammation and if so, how it influences the course of inflammation. These efforts have led to the discovery of cytokine-like activities of rhSAA, which is commercially available and widely used in most of the published studies. SAA activates multiple receptors, including the FPR2, the TLRs TLR2 and TLR4, the scavenger receptor SR-BI, and the ATP receptor P2X7. More recent studies have shown that SAA not only activates transcription factors, such as NF-κB, but also plays a role in epigenetic regulation through a MyD88-IRF4-Jmjd3 pathway. It is postulated that the activation of these pathways leads to induced expression of proinflammatory factors and a subset of proteins expressed by the M2 macrophages. These functional properties set SAA apart from well-characterized inflammatory factors, such as LPS and TNF-α, suggesting that it may play a homeostatic role during the course of inflammation. Ongoing and future studies are directed to addressing unresolved issues, including the difference between rSAA and native SAA isoforms and the exact functions of SAA in physiologic and pathologic settings.
authors.affiliation: *School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; and Department of Pharmacology, University of Illinois at Chicago, Illinois, USA ye.richard@outlook.com.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.affiliation: *School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; and Department of Pharmacology, University of Illinois at Chicago, Illinois, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology* / Q000473:pathology; D000255:Adenosine Triphosphate / Q000276:immunology; D000818:Animals; D006801:Humans; D050835:Interferon Regulatory Factors / Q000276:immunology; D056484:Jumonji Domain-Containing Histone Demethylases / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D058486:Receptors, Purinergic P2X7 / Q000276:immunology; D051122:Scavenger Receptors, Class B / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D000255:Adenosine Triphosphate; D050835:Interferon Regulatory Factors; D056484:Jumonji Domain-Containing Histone Demethylases; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D058486:Receptors, Purinergic P2X7; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099218:Interferon Regulatory Factor-4; C507779:MYD88 protein, human; C546468:P2RX7 protein, human; C495124:SCARB1 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C524220:KDM6B protein, human
keywords: acute-phase reactants; cytokines; epigenetic regulation; stress response