Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation.

TLDR

The hepatic acute‑phase response is a coordinated up‑regulation of essential plasma proteins driven by cytokines (IL‑1, TNFα, IL‑6), hepatocyte‑stimulating factor‑III, and corticosteroids, with expression levels modulated by the pre‑existing and changing hepatic hormonal milieu. The study aims to predict the hepatic phenotype during acute and chronic inflammation by determining how glucocorticoids, IL‑1, and PKC activation influence cytokine‑mediated liver responses and how the hepatic environment modulates these effects. The authors investigate the specific effects of glucocorticoids, IL‑1, and protein kinase C activation on hepatic acute‑phase gene expression.

Abstract

The hepatic response to systemic injury is characterized by a co-ordinated increase in the expression of several, functionally essential plasma proteins. The factors responsible for initial hepatic stimulation have been identified and include the cytokines IL-1 (interleukin-1), tumor necrosis factor alpha (TNF alpha), IL-6 (interleukin-6), hepatocyte-stimulating factor-III (HSF-III) as well as corticosteroids. The absolute level of expression of the regulated proteins appears to be modulated by the pre-existing hepatic hormonal environment and changes to that environment that occur during acute phase reactions. The specific effects of glucocorticoids, IL-1 and activation of protein kinase C are addressed in this study. In order to predict the phenotype of liver response in acute phase, the hepatic activities of all inflammatory cytokines present must be established. Moreover, it must be recognized that the hepatic environment itself can modulate the anabolic response of the liver to these cytokines. The same considerations are needed when determining the changes seen during the progression to chronic inflammation.