Role of Glucocorticoid in the Upregulation of Type I Interleukin-1 Receptor mRNA Expression in Hepatocytes of Endotoxin-Administrated Mice

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Abstract
The interleukin-1 (IL-1) signal is transduced through type I IL-1 receptor (IL-1RI). We have recently reported that lipopolysaccharide (LPS) upregulated IL-1RI mRNA expression in mouse liver in vivo and that IL-1 and IL-6 directly upregulated IL-1RI mRNA expression in primary cultured mouse hepatocytes. Glucocorticoid (GC) has been reported to increase IL-1 binding to the cell surface and the expression level of IL-1R mRNA in a variety of cell types. As serum GC level is elevated in an inflammatory response, we evaluated the role of GC in LPS-induced upregulation of IL-1RI mRNA in the mouse liver. When LPS was administered to adrenalectomized (ADX) mice, IL-1RI mRNA was upregulated at a level comparable to those of untreated or sham-operated mice. A high dose of dexamethasone (Dex), however, caused upregulation of the mRNA. When primary cultured mouse hepatocytes were treated with Dex, only a weak upregulation of IL-1RI mRNA was observed. However, Dex in combination with IL-1 or IL-6 markedly enhanced the IL-1RI mRNA expression. A marked upregulation of the mRNA was also induced by treatment with a combination of IL-1 and IL-6 in the absence of Dex, reflecting the observation in ADX mice. These results suggest that the upregulation of IL-1RI mRNA in response to LPS is induced by the interaction of IL-1 and IL-6 and that GC augments their effect.