Role of glucocorticoid in the upregulation of type I interleukin-1 receptor mRNA expression in hepatocytes of endotoxin-administrated mice.
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.
Ito
A
A
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Takii
T
T
Goto
N
N
Kito
Y
Y
Onozaki
K
K
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000096:biosynthesis*; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D003907:Dexamethasone