Premium
Coordinated regulation of ceruloplasmin and metallothionein mRNA by interleukin‐1 and copper in HepG2 cells
Author(s) -
Daffada Angela A.I,
Young Stephen P
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01036-4
Subject(s) - metallothionein , ceruloplasmin , messenger rna , acute phase protein , chemistry , microbiology and biotechnology , copper , interleukin , endocrinology , medicine , biology , biochemistry , immunology , cytokine , inflammation , gene , organic chemistry
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‐1α, IL‐1β 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‐1α and IL‐1β 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‐1β, whereas IL‐1α 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.