Role of Fetuin-A in Injury and Infection

Abstract

Injury and infection, seemingly unrelated conditions, converge on a common process inflammation, which is mediated partly by innate immune cells including macrophages and monocytes. These innate immune cells are equipped with pattern recognition receptors (such as TLR2, TLR4, and TLR9) (Brightbill et al. 1999; Poltorak et al. 1998; Hemmi et al. 2000), and can recognize both damageand pathogen-associated molecular patterns (DAMPs, such as HMGB1; and PAMPs, such as endotoxin) (Andersson et al. 2000; Chen et al. 2009;Krieg 2002;Wang et al. 1999;Ivanov et al. 2007). In response to various PAMPs or DAMPs, innate immune cells release proinflammatory cytokines (such as TNF, IL-1, IFN-┛ or HMGB1 to mount inflammatory responses. If dysregulated, an uncontrolled inflammation may adversely lead to detrimental consequences. To orchestrate the inflammatory response to infection and injury, the liver strategically re-prioritizes the synthesis and systemic release of a group of proteins collectively termed “acute phase proteins” (APPs). For instance, fetuin-A, also called the alpha-2-HS-glycoprotein for the human homologue (Christie et al. 1987), has been implicated as an anti-inflammatory protein during injury or infections. In this book chapter, we summarize emerging evidence to support fetuin-A as an acute phase protein capable of attenuating injuryor infection-elicited inflammatory responses.