Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells

L. Bartalena, G. L. Hammond, A. Farsetti, I. L. Flink, J. Robbins

Research output: Contribution to journalArticle

Abstract

Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include α1-antitrypsin, α1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases α1-antitrypsin and α1-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 eiposed 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.

Original languageEnglish
Pages (from-to)291-296
Number of pages6
JournalEndocrinology
Volume133
Issue number1
Publication statusPublished - Jul 1993

Fingerprint

Transcortin
Hepatoblastoma
Hep G2 Cells
Interleukin-6
Globulins
Culture Media
Messenger RNA
Serine Proteinase Inhibitors
RNA Stability
Neutralizing Antibodies
Methionine
Biological Availability
Hydrocortisone
Cytokines

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Bartalena, L., Hammond, G. L., Farsetti, A., Flink, I. L., & Robbins, J. (1993). Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. Endocrinology, 133(1), 291-296.

Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. / Bartalena, L.; Hammond, G. L.; Farsetti, A.; Flink, I. L.; Robbins, J.

In: Endocrinology, Vol. 133, No. 1, 07.1993, p. 291-296.

Research output: Contribution to journalArticle

Bartalena, L, Hammond, GL, Farsetti, A, Flink, IL & Robbins, J 1993, 'Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells', Endocrinology, vol. 133, no. 1, pp. 291-296.
Bartalena L, Hammond GL, Farsetti A, Flink IL, Robbins J. Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. Endocrinology. 1993 Jul;133(1):291-296.
Bartalena, L. ; Hammond, G. L. ; Farsetti, A. ; Flink, I. L. ; Robbins, J. / Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. In: Endocrinology. 1993 ; Vol. 133, No. 1. pp. 291-296.
@article{59912bf641e042d3bc9caffd105e9f24,
title = "Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells",
abstract = "Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include α1-antitrypsin, α1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases α1-antitrypsin and α1-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 eiposed 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.",
author = "L. Bartalena and Hammond, {G. L.} and A. Farsetti and Flink, {I. L.} and J. Robbins",
year = "1993",
month = "7",
language = "English",
volume = "133",
pages = "291--296",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells

AU - Bartalena, L.

AU - Hammond, G. L.

AU - Farsetti, A.

AU - Flink, I. L.

AU - Robbins, J.

PY - 1993/7

Y1 - 1993/7

N2 - Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include α1-antitrypsin, α1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases α1-antitrypsin and α1-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 eiposed 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.

AB - Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include α1-antitrypsin, α1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases α1-antitrypsin and α1-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 eiposed 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.

UR - http://www.scopus.com/inward/record.url?scp=0027179189&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027179189&partnerID=8YFLogxK

M3 - Article

C2 - 8391424

AN - SCOPUS:0027179189

VL - 133

SP - 291

EP - 296

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 1

ER -