Coordinated regulation of ceruloplasmin and metallothionein mRNA by interleukin-1 and copper in HepG2 cells

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

During the acute phase response, cytokines induce hepatic metallothionein and ceruloplasmin synthesis and the uptake of metals. We have investigated how copper and cytokines may interact in controlling ceruloplasmin (CP) and metallothionein mRNA in liver cells. We found that IL-1alpha, IL-1beta and IL-6 increased both metallothionein-1 (MT-1) and metallothionein-2 (MT-2) mRNA in HepG2 cells. The time and pattern of induction was different, both IL-1alpha and IL-1beta inducing two peaks of MT-1 and MT-2, with that of MT-2 being much larger. IL-6 induced only low levels of both MT-1 and MT-2 mRNA. CP mRNA was also increased after 16 h by IL-1beta, whereas IL-1alpha induced two CP peaks at 8 and 20 h, while IL-6 had little effect. Copper administration gave rise to substantially increased MT-1 mRNA, a slightly lower increase in MT-2 and also a significant increase in CP mRNA with similar kinetics. These parallel increases in MT and CP mRNA suggest that the coordinated expression of these proteins may be important for their synthesis during the acute phase response.

Details

Original languageEnglish
Pages (from-to)214-8
Number of pages5
JournalFEBS Letters
Volume457
Issue number2
Publication statusPublished - 27 Aug 1999

Keywords

  • RNA, Messenger, Tumor Cells, Cultured, Metallothionein, Interleukin-1, Humans, Ceruloplasmin, Interleukin-6, Gene Expression Regulation, Copper