Activin A regulates growth and acute phase proteins in the human liver cell line, HepG2

Mol Cell Endocrinol. 1999 Feb 25;148(1-2):129-36. doi: 10.1016/s0303-7207(98)00226-3.


Activin, and its binding protein, follistatin, are up-regulated by mediators of inflammation, and recent studies have demonstrated that activin A can block the activity of the key inflammatory cytokine, interleukin-6 (IL-6). These findings thereby implicate activin and follistatin in the control of the inflammatory cascade. In this study, interactions between interleukin-1beta (IL-1beta), IL-6 and activin were examined the human liver cell line, HepG2, for their effect on cell proliferation and the production of the acute phase proteins, haptoglobin and alpha1-acid glycoprotein (alpha1-AGP). IL-1beta and activin A, but not IL-6, inhibited the proliferation of HepG2 cells. Activin A together with IL-1beta caused a greater inhibition of proliferation than either factor alone, and the inhibitory effects of activin A were blocked by the addition of follistatin to the cultures. Activin A alone inhibited the production of haptoglobin but did not affect alpha1-AGP concentrations. However, activin A suppressed the stimulatory effects of IL-6 on the production of both haptoglobin and alpha1-AGP. Production of follistatin by HepG2 cells was stimulated by activin A, but was inhibited by both IL-1beta and IL-6, indicating a complex regulatory loop is operable to modulate the effects of activin A during inflammation. Taken together, these data suggest that activin A interacts with IL-1beta and IL-6 to regulate and coordinate the production of acute phase proteins during an inflammatory episode.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins
  • Acute-Phase Proteins / biosynthesis*
  • Carcinoma, Hepatocellular
  • Cell Division / drug effects*
  • Dose-Response Relationship, Drug
  • Follistatin
  • Glycoproteins / pharmacology
  • Growth Substances / pharmacology
  • Haptoglobins / biosynthesis
  • Humans
  • Inflammation
  • Inhibins / antagonists & inhibitors
  • Inhibins / pharmacology*
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology*
  • Kinetics
  • Liver Neoplasms
  • Orosomucoid / biosynthesis
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured


  • Acute-Phase Proteins
  • Follistatin
  • Glycoproteins
  • Growth Substances
  • Haptoglobins
  • Interleukin-1
  • Interleukin-6
  • Orosomucoid
  • Recombinant Proteins
  • Activins
  • Inhibins