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Metallothionein Expression in Rat Bone Marrow Is Dependent on Dietary Zinc but not Dependent on Interleukin-1 or Interleukin-6¹

Center for Nutritional Sciences, University of Florida, Gainesville, FL 32611

The comparative influence of dietary zinc status and recombinant human interleukin-1 (rhIL-1) and recombinant human interleukin-6 (rhIL-6) on metallothionein (MT) gene expression was examined in rat bone marrow and liver. Growing male rats were fed a diet with 5 (restricted), 30 (control), or 180 (supplemented) mg Zn/kg for 14 d. On d 15, rats were injected with 5 µg of rhIL-1 or rhIL-6. Marrow metallothionein responded directly to dietary zinc but did not respond to these cytokines. Significantly less zinc accumulated in marrow from the zinc-restricted rats compared with control or supplemented rats. Analysis of metallothionein isoform mRNA expression showed MT-1 is the primary gene expressed in marrow. A significant interaction between dietary zinc and cytokine treatment was observed in the liver. Hepatic metallothionein induction following both rhIL-1 and rhIL-6 injection was directly related to dietary zinc intake. Expression of hepatic metallothionein isoform mRNAs suggested MT-1 responded to zinc and MT-2 responded to cytokines. These results indicate that metallothionein gene expression in both the marrow and the liver responds to dietary zinc status. In contrast, liver metallothionein expression can be altered by these cytokines, which are known to act on many cell types. Furthermore, these results suggest that bone marrow metallothionein could be of importance in the development of marrow cells.

KEY WORDS: • metallothionein gene • hematopoiesis • rats • zinc • cytokine

¹ Supported by National Institutes of Health research grant no. DK 31127 and Boston Family Endowment Funds.

² Supported by fellowship from a Center of Excellence Award from Pew National Nutrition Program. Current address: School of Medicine, University of Miami, Miami, FL.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 6 August 1992. Revision accepted 2 December 1992.

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