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Metallothionein synthesis induced by interferon alpha/beta in mice of various zinc status
Abstract:
We studied the ability of interferon alpha/beta (IFN) to induce metallothionein (MT) synthesis in mice. Male mice were injected intraperitoneally with mouse IFN (5 x 10(5) IU/mouse). Plasma Zn levels were reduced at 4 hr after injection, reached a minimum value at 6 hr, and then returned to the control level at 8 hr. Hepatic MT concentrations began to increase at 4 hr and reached maximum values at 6 hr. Induction of MT gene expression and protein synthesis was confirmed by Northern blot analysis and radioimmunoassay, respectively. The induction of MT synthesis in the liver by IFN was dose-dependent. The data suggest that induction of MT-mRNA and the protein in the liver by IFN occurs rapidly but is rather transient. Furthermore, MT synthesis was not induced by IFN in the liver of mice given a Zn-deficient diet, whereas IFN induced increases in the activity of 2',5'-oligoadenylate synthetase in the spleen were unaffected by Zn status. Thus, induction of hepatic MT synthesis by IFN is influenced by Zn status.
Insights
Interferon (IFN) rapidly induces metallothionein (MT) synthesis in mouse liver, but this effect is transient and depends on zinc availability. Zinc deficiency blocks IFN-induced MT synthesis.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Interferon alpha/beta (IFN) is a key mediator of the innate immune response.
- Metallothioneins (MTs) are small, cysteine-rich proteins involved in heavy metal homeostasis and protection against oxidative stress.
Purpose of the Study:
- To investigate the ability of interferon alpha/beta (IFN) to induce metallothionein (MT) synthesis in mice.
- To determine the kinetics and zinc dependency of IFN-induced MT synthesis.
Main Methods:
- Intraperitoneal injection of mouse IFN in male mice.
- Measurement of plasma zinc levels.
- Quantification of hepatic MT concentrations using Northern blot analysis and radioimmunoassay.
- Assessment of IFN-induced 2',5'-oligoadenylate synthetase activity in spleen.
Main Results:
- IFN injection led to a rapid, transient decrease in plasma zinc levels and a corresponding rapid, transient increase in hepatic MT concentrations.
- MT induction by IFN was dose-dependent and confirmed at both mRNA and protein levels.
- IFN-induced hepatic MT synthesis was abolished in mice on a zinc-deficient diet, while splenic 2',5'-oligoadenylate synthetase activity remained unaffected.
Conclusions:
- Interferon alpha/beta rapidly induces metallothionein synthesis in the liver, which is a transient process.
- Hepatic metallothionein induction by IFN is critically dependent on zinc status.
- These findings highlight the interplay between immune signaling and metal metabolism.