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Hepatic acute phase proteins--regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-κB-dependent signaling

Abstract:

The function of the liver as an important constituent of the immune system involved in innate as well as adaptive immunity is warranted by different highly specialized cell populations. As the major source of acute phase proteins, including secreted pathogen recognition receptors (PRRs), short pentraxins, components of the complement system or regulators of iron metabolism, hepatocytes are essential constituents of innate immunity and largely contribute to the control of a systemic inflammatory response. The production of acute phase proteins in hepatocytes is controlled by a variety of different cytokines released during the inflammatory process with IL-1- and IL-6-type cytokines as the leading regulators operating both as a cascade and as a network having additive, inhibitory, or synergistic regulatory effects on acute phase protein expression. Hence, IL-1β substantially modifies IL-6-induced acute phase protein production as it almost completely abrogates production of acute phase proteins such as γ-fibrinogen, α(2)-macroglobulin or α(1)-antichymotrypsin, whereas production of for example hepcidin, C-reactive protein and serum amyloid A is strongly up-regulated. This switch-like regulation of IL-6-induced acute phase protein production by IL-1β is due to a complex processing of the intracellular signaling events activated in response to IL-6 and/or IL-1β, with the crosstalk between STAT3- and NF-κB-mediated signal transduction being of particular importance. Recent data suggest that in this context complex formation between STAT3 and the p65 subunit of NF-κB might be of key importance. The present review summarizes the regulation of acute phase protein production focusing on the role of the crosstalk of STAT3- and NF-κB-driven pathways for transcriptional control of acute phase gene expression.

22093287

Projects: B1.1: Differential communication of wound healing and hepatoxic macropha..., B1.2: Reciprocal effect of cell-cell communication on information proces..., D2: Dynamics of metabolism, inflammation and ammonia detoxication during..., D3: Inflammation and Regeneration: the whole organ

Eur. J. Cell Biol.
Eur. J. Cell Biol. 91(6-7): 496-505
16th Nov 2011

Johannes G Bode, Ute Albrecht, Dieter Häussinger, Peter C Heinrich, Fred Schaper

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[Johannes Bode] [Ute Albrecht] [Dieter Häussinger]

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Cell and Liver
Views: 1820
  • Created: 31st Aug 2012 at 11:44
  • Last updated: 24th Oct 2013 at 16:17

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