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-de rived 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 l evels transiently increased in mice following an acute inflammatory stimulu s. We now report that IL-6, a major inducer of acute-phase proteins, stimul ates 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-li fe. This increase, suppressible by cycloheximide, peaks at 12 hr following stimulation and returns to basal levels by 48 hr, IL-1 alone slightly decre ases the basal production of angiogenin protein and mRNA, but essentially a bolishes 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 change s 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 i s regulated in a manner similar to that of acute phase proteins both in vit ro and in vivo, it may play a role in the host response to injury. (C) 1999 Academic Press.