Premium
Inhibition of erythropoietin production in vitro by human interferon gamma
Author(s) -
Vannucchi A. M.,
Grossi A.,
Rafanelli D.,
Statello M.,
Cinotti S.,
RossiFerrini P.
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb04864.x
Subject(s) - erythropoietin , in vitro , cytokine , hep g2 , cell culture , medicine , interferon gamma , endocrinology , interferon , northern blot , chemistry , tumor necrosis factor alpha , inhibitory postsynaptic potential , microbiology and biotechnology , biology , immunology , messenger rna , biochemistry , gene , genetics
Summary The effects of interferon‐gamma (IFN‐γ). alone and in combination with IL‐1, IL‐6 and tumour necrosis factor‐alpha (TNF‐α), on in vitro erythropoietin (Epo) production by the human hepatoma Hep 3B cell line were evaluated. The addition of IFN‐γ to either unstimulated or cobalt chloride (CoCl 2 )‐treated Hep 3B cells resulted in a dosedependent inhibition of Epo release in the medium by as much as 70% at 1000 U/ml. Half‐maximal inhibition was observed at around 50 U/ml. According to previous observations, IL‐6 had a stimulatory effect on Epo production by CoCl 2 ‐treated Hep3B cells: however, the simultaneous addition of IFN‐γ and IL‐6 resulted in a reversal of the stimulatory effects due to IL‐6. IFN‐γ and IL‐1 had an additive inhibitory effect, whereas IFN‐γ and TNF‐α acted in a synergistic fashion in inhibiting Epo production by Hep 3B cells. The inhibitory effect of IFN‐γ appeared to be due to a down‐modulation of Epo mRNA levels in CoCl 2 ,‐treated Hep 3B cells, as shown by Northern blot analysis. These data indicate that Epo production by hepatoma cells in vitro is inhibited by IFN‐γ, and that a complex network of interacting cytokines may regulate Epo production in response to an hypoxic stimulus. Overall, these results also suggest that IFN‐γ might have a role in the defective Epo production observed in several inflammatory and immunemediated disorders characterized by relatively high IFN‐γ plasma levels.