title: Regulation of acute phase protein genes by hepatocyte-stimulating factors, monokines and glucocorticoids.
abstract: The synthesis of all the major acute phase plasma proteins is stimulated in rat hepatoma and primary cultures of hepatocytes by three, structurally and functionally distinct groups of hormones: 1) hepatocyte-stimulating factors (HSF) and interleukin-6 (IL-6); 2) interleukin-1 (IL-1) and tumor necrosis factor (TNF); and 3) glucocorticoids. Each plasma protein gene requires a specific combination of these 3 hormone types for maximal expression. One set of acute phase proteins, including alpha 2-macroglobulin, alpha 1-antichymotrypsin ( = contrapsin), cysteine protease inhibitor ( = thiostatin), alpha 1-antitrypsin, ceruloplasmin and fibrinogens are predominantly regulated by the keratinocyte-derived HSF-III/-II or IL-6, while a second set of proteins, including alpha 1-acid glycoprotein (AGP), haptoglobin and complement C3 are predominantly regulated by keratinocyte-derived HSF-I, IL-1 or TNF. In conjunction with the above peptide hormones, glucocorticoids synergistically enhance the stimulated expression of most, but not all, acute phase proteins. An exceptionally strong synergy between HSF (or IL-6), IL-1 and glucocorticoids is noted for the activation of the AGP gene. To elucidate the molecular mechanisms of regulation, we have identified the cis-acting genetic elements through which all these hormones control the transcriptional activity of the AGP gene. It appears that acute phase activates a specific nuclear binding protein in the rat liver that interacts with the peptide hormone responsive element located 5 kb upstream of the transcriptional start site.
authors: Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.
authors: H
authors: H
authors: Baumann
authors: K R
authors: KR
authors: Prowse
authors: K A
authors: KA
authors: Won
authors: S
authors: S
authors: Marinković
authors: G P
authors: GP
authors: Jahreis
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D005809:Genes, Regulator; D005938:Glucocorticoids / Q000494:pharmacology*; D015850:Interleukin-6; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D015846:Monokines / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D015183:Restriction Mapping
chemical_list: D000209:Acute-Phase Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D015846:Monokines; D011506:Proteins