Cytokine regulation of gut ornithine decarboxylase gene expression and enzyme activity.

Abstract

The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis and is important for gut mucosal repair after systemic injury (e.g., burns); however, the mechanisms responsible for the injury-mediated induction of ODC are not known. The purpose of this study was to determine whether interleukin-1 (IL-1) or tumor necrosis factor (TNF), which are released immediately after injury, regulates gut mucosal ODC enzyme activity and gene expression. In vivo: In experiment 1, 64 male BALB/c mice received either recombinant IL-1 beta (2 x 10(4) units/kg administered intraperitoneally) or saline solution. In experiment 2, 64 mice received either recombinant TNF-alpha (100 micrograms/kg administered intraperitoneally) or saline solution. We determined ODC enzyme activity and ODC mRNA levels in small intestine and kidneys at 2, 4, 12, and 24 hours after injection. In vitro: We also determined the ODC enzyme activity in intestinal epithelial crypt cells after either IL-1 beta or TNF-alpha treatment. IL-1, but not TNF, increased small intestinal ODC enzyme activity. In addition, IL-1 increased ODC enzyme activity in intestinal epithelial crypt cells at 5 and 6 hours after treatment. Both IL-1 and TNF increased small intestinal ODC mRNA levels. Neither agent affected ODC enzyme activity or ODC mRNA levels in the kidney. These results suggest that the cytokine-mediated induction of ODC in the small intestine is tissue specific, that the induction occurs at multiple cellular levels, and that ODC may play a vital role in the restoration of gut mucosa that occurs after injury.