Z Gastroenterol 2012; 50 - P3_18
DOI: 10.1055/s-0031-1295860

Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase-response

IA Malik 1, J Triebel 1, J Posselt 1, P Ramadori 1, D Raddatz 1, G Ramadori 1
  • 1Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen

Melanocortin receptors (MCRs) are known to be expressed predominantly in the brain where they exert metabolic and anti-inflammatory functions. Furthermore, the brain MCRs are supposed to also mediate anti-inflammatory effects in other organs. As serum levels of MCRs-ligands are elevated in clinical situation (acute-phase-response (APR)) of tissue damage, we studied hepatic gene expression of MCRs in a model of muscle tissue damage induced by turpentine-oil (TO) injection in rats. A significant increase in gene expression of all five MCRs (MC4R was the highest) in liver at the RNA and protein level was detected after TO-injection. A similar pattern of increase was also found in brain. Immunohistology showed MC4R in the cytoplasm but also in the nucleus of parenchymal and non-parenchymal liver cells whereas MC3R-postivity was mainly cytoplasmic. A time-dependent migration of MC4R protein from the cytoplasm into the nucleus was observed during APR in parallel with an increase in α-MSH and leptin serum level. An increase of MC4R was detected at protein level in Wild type mice, while such an increase was not observed in IL–6ko mice during APR. Moreover, treatment of isolated liver cells with melanocortin-agonists (α-MSH and THIQ) inhibited the endotoxin-induced upregulation of the acute-phase-cytokines (IL–6, IL1β and TNF-α) gene expression in Kupffer cells and of chemokines gene expression in hepatocytes. MCRs are expressed not only in the brain but also in liver cells and their gene expression in liver and brain tissue is upregulated during APR. Due to presence of specific ligands in the serum, they may exert a protective effect in liver cells without involvement of the brain receptors.