Abstract
The expression of acute-phase proteins (APP's) maintains homeostasis and tissue repair, but also represents a central component of the organism's defense strategy, especially in the context of innate immunity. Accordingly, an inflammatory response is accompanied by significant changes in the serum protein composition, an aspect that is also used diagnostically. As the main site of APP synthesis the liver is constantly exposed to antigens or pathogens via blood flow, but also to systemic inflammatory signals originating either from the splanchnic area or from the circulation. Under both homeostatic and acute-phase response (APR) conditions the composition of APP's is determined by the pattern of regulatory mediators derived from the systemic circulation or from local cell populations, especially liver macrophages. The key regulators mentioned here most frequently are IL-1β, IL-6 and TNF-α. In addition to a variety of molecular mediators described mainly on the basis of in vitro studies, recent data emphasize the in vivo relevance of cellular key effectors as well as molecular key mediators and protein modifications for the regulation and function of APP's. These are aspects, on which the present review is primarily focused.
Highlights
The electrophoretic separation of serum proteins has an established place worldwide in clinical diagnostics in both human and veterinary medicine (Alper 1974; Moore and Avery 2019)
In a model of acutephase response (APR) induced by LPS as well as in a model of polymicrobial sepsis by cecal ligation and puncture (CLP) blockade of gp130/ signal transducer and activator of transcription 3 (STAT3)-mediated signaling in hepatocytes and consequent synthesis of acute-phase proteins (APP’s) leads to impaired survival and significant increase in serum concentrations of inflammatory cytokines such as IL-6, tumor necrosis factor (TNF)-α, and IFN-γ (Sander et al 2010)
NFκB/reticuloendotheliosis viral oncogene homolog A (RelA), known as subunit protein with 65 kDa in size (p65), in hepatocytes plays a regulatory role in the context of systemic inflammatory processes as it balances APP expression and provides hepatoprotection in sepsis or pneumonia by attenuating TNF-α-mediated immunotoxicity
Summary
The electrophoretic separation of serum proteins has an established place worldwide in clinical diagnostics in both human and veterinary medicine (Alper 1974; Moore and Avery 2019). With regard to the regulation of APP synthesis the central localization of the liver, its specific architecture and its cellular composition play an important role, since the production of these proteins by hepatocytes occurs in response to systemic and/or locally delivered intercellular communication signals, in particular a number of cytokines.
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