Activin A regulates growth and acute phase proteins in the human liver cell line, HepG2.
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.
Russell
C E
CE
Institute of Reproduction and Development, Monash Medical Centre, Monash University, Clayton Victoria, Australia.
Hedger
M P
MP
Brauman
J N
JN
de Kretser
D M
DM
Phillips
D J
DJ
D028341:Activins; D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006242:Haptoglobins / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D007265:Inhibins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D009961:Orosomucoid / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D006242:Haptoglobins; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins