QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coyle, P. Articles by Rofe, A. M. Search for Related Content PubMed PubMed Citation Articles by Coyle, P. Articles by Rofe, A. M.

Corticosterone Enhances the Zinc and Interleukin-6-Mediated Induction of Metallothionein in Cultured Rat Hepatocytes¹

Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, SA 5000 Australia

The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10–50 µmol/L). Dexamethasone at 1 µmol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 µmol/L Zn and 1 µmol/L dexamethasone. Interleukin-6 (1 x 10⁵ U/L) alone did not induce metallothionein but increased it 35–65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was 100 times more potent than corticosterone at 10–100 µmol/L. Physiological concentrations of corticosterone (1 µmol/L) when added alone, with Zn (10 µmol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 µmol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 µmol/L)+dexamethasone (1 µmol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1ß, tumor necrosis factor or interferon (1 x 10⁵ U/L) alone, but interleukin-1ß and tumor necrosis factor enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1ß+tumor necrosis factor +interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin-6. The roles of other cytokines and glucagon demonstrate the multifactorial nature of metallothionein regulation.

KEY WORDS: • rats • metallothionein • corticosterone • interleukin-6 • hepatocytes

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

² To whom correspondence and reprint requests should be addressed.

Manuscript received 3 November 1992. Revision accepted 27 April 1993.

This article has been cited by other articles:

				J. Hernandez, J. Carrasco, M.L. Arbones, and J. Hidalgo IFN-{gamma}R -/- mice show an enhanced liver and brain metallothionein I+II response to endotoxin but not to immobilization stress Innate Immunity, October 1, 1997; 4(5): 363 - 370. [Abstract] [PDF]