Regulation of angiogenin expression in human HepG2 hepatoma cells by mediators of the acute-phase response.
Angiogenin is a potent inducer of neovascularization in vivo. However, like other angiogenic molecules, its specific physiologic roles and mechanisms regulating its expression remain to be elucidated. Angiogenin is a liver-derived component of normal serum whose concentration can increase in various disease states. This suggests that it might participate in the acute-phase response. In an initial study we showed that angiogenin protein and mRNA levels transiently increased in mice following an acute inflammatory stimulus. We now report that IL-6, a major inducer of acute-phase proteins, stimulates the synthesis and secretion of angiogenin protein in human HepG2 cells within 24 hr following treatment, an effect enhanced by dexamethasone. IL-6 also increases the amount of angiogenin mRNA without altering its half-life. This increase, suppressible by cycloheximide, peaks at 12 hr following stimulation and returns to basal levels by 48 hr. IL-1 alone slightly decreases the basal production of angiogenin protein and mRNA, but essentially abolishes the response to IL-6 in the absence or presence of dexamethasone. This antagonistic effect by IL-1 on IL-6 activity is not a result of changes in mRNA stability nor is it dependent on new protein synthesis. Thus, the combined effects of IL-6, IL-1, glucocorticoids, and perhaps other related factors may specifically control angiogenin expression. Since angiogenin is regulated in a manner similar to that of acute phase proteins both in vitro and in vivo, it may play a role in the host response to injury.
Verselis
S J
SJ
Center for Biochemical and Biophysical Sciences and Medicine, Department of Pathology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts, 02115, USA.
Olson
K A
KA
Fett
J W
JW
D000209:Acute-Phase Proteins / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012259:Ribonuclease, Pancreatic; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011506:Proteins; D012333:RNA, Messenger; D005340:Fibrinogen; C046366:angiogenin; D012259:Ribonuclease, Pancreatic