Anti-Inflammatory Role of Fetuin-A in Injury and Infection

Author(s): H. Wang, A. E. Sama

Journal Name: Current Molecular Medicine

Volume 12 , Issue 5 , 2012

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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.

Keywords: Acute phase protein, cerebral ischemic injury, DAMP, endotoxemia, HMGB1, innate immune cells, PAMP, sepsis.

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Article Details

Year: 2012
Published on: 06 May, 2012
Page: [625 - 633]
Pages: 9
DOI: 10.2174/156652412800620039
Price: $65

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