ZINC-DEFICIENCY ENHANCES INTERLEUKIN-1-ALPHA-INDUCED METALLOTHIONEIN-1 EXPRESSION IN RATS

This study investigated whether interleukin-1 alpha-induced metallothi onein gene expression is affected by zinc deficiency. Weaning male rat s were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplem ented diet [50.8 mg zinc/kg; controls for the diet included pair-fed ( PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1 alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutane ously with interleukin-1 alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly red uced hepatic, renal, and intestinal metallothionein-1 mRNA levels anal yzed by competitive reverse transcription-polymerase chain reaction (R T-PCR). Interleukin-1 alpha injection reduced plasma zinc concentratio n and enhanced liver zinc concentration, but did not affect zinc level s in kidney or intestine. Metallothionein-l mRNA was significantly ele vated by interleukin-1 alpha in liver, kidney and intestine of all gro ups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallot hionein protein levels were enhanced after interleukin-1 alpha injecti on in both AL and ZD rats. Semiquantitative RT-PCR revealed significan tly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1 alpha challenge. In conclusi on, zinc deficiency induces upregulation of metallothionein-1 gene exp ression in response to interleukin-1 alpha challenge in rats.