Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells.
Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include alpha 1-antitrypsin, alpha 1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases alpha 1-antitrypsin and alpha 1-antichymotrypsin synthesis and decreases T4-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. This effect is predominantly at a transcriptional level. When Hep G2 cells were exposed to different concentrations of IL-6 for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the amount of [35S]methionine-labeled CBG immunoprecipitated in the culture medium. This effect could be greatly reduced by preincubation of IL-6 with its neutralizing antibody and reversed by removing the cytokine from the culture medium. The secretion rate of CBG was not affected by cell exposure to IL-6. CBG mRNA steady state levels were reduced; changes in mRNA were quantitatively similar to changes in secreted protein. Nuclear run-off assays failed to show a change in the rate of transcription of the CBG gene. These data indicate that IL-6 diminishes CBG synthesis by Hep G2 cells acting at a posttranscriptional level, presumably through a reduced stability of mRNA. In view of the role of IL-6 in the inflammatory process and other acute phase phenomena, these data suggest that its effects on CBG synthesis might influence the bioavailability of cortisol indirectly and play a role in regulating the homeostatic process during these conditions.
Istituto di Endocrinologia, University of Pisa, Italy.
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L
Bartalena
G L
GL
Hammond
A
A
Farsetti
I L
IL
Flink
J
J
Robbins
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014156:Transcortin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D015850:Interleukin-6; D012333:RNA, Messenger; D014156:Transcortin