title: Anti-inflammatory role of fetuin-A in injury and infection.
abstract: Infection and injury are two seemingly unrelated processes that often converge on common innate inflammatory responses mediated by pathogen- or damage-associated molecular patterns (PAMPs or DAMPs). If dysregulated, an excessive inflammation manifested by the overproduction and release of proinflammatory mediators (e.g., TNF, IFN-γ, and HMGB1) may adversely lead to many pathogenic consequences. As a counter-regulatory mechanism, the liver strategically re-prioritizes the synthesis and systemic release of acute phase proteins (APP) including the fetuin-A (also termed alpha-2-HS-glycoprotein for the human homologue). Fetuin-A is divergently regulated by different proinflammatory mediators, and functions as a positive or negative APP in injury and infection. It not only facilitates anti-inflammatory actions of cationic polyamines (e.g., spermine), but also directly inhibits PAMP-induced HMGB1 release by innate immune cells. Peripheral administration of fetuin-A promotes a short-term reduction of cerebral ischemic injury, but confers a long-lasting protection against lethal endotoxemia. Furthermore, delayed administration of fetuin-A rescues mice from lethal sepsis even when the first dose is given 24 hours post the onset of disease. Collectively, these findings have reinforced an essential role for fetuin-A in counter-regulating injury- or infection-elicited inflammatory responses.
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, North Shore- LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA. hwang@nshs.edu
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: A E
authors.initials: AE
authors.lastname: Sama
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein / Q000276:immunology / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D024243:HMGB1 Protein; D060749:alpha-2-HS-Glycoprotein