Endotoxin-induced upregulation of type I interleukin-1 receptor mRNA expression in hepatocytes of mice: Role of cytokines

Interleukin-1 (IL-1) signal is transduced through the type I IL-1 receptor (IL-1RI). Although regulation of IL-1R expression has been extensively studied in vitro, little is known about it in vivo. By using RT-PCR analysis, we investigated the regulation of the IL-1RI mRNA expression level in various organs of mice at 2, 6, and 24 h following lipopolysaccharide (LPS) administration, IL-1RI mRNA expression in response to LPS appeared to be different in various organs, As a marked and sustained increase of IL-1RI mRNA expression in the liver was observed, we investigated the mechanism of the upregulation, IL-1, IL-6, and tumor necrosis factor (TNF) all increased the mRNA expression in the liver when administrated in vivo, In situ hybridization revealed that upregulation of IL-1R mRNA was observed in parenchymal liver cells (hepatocytes) in response to LPS administration, When primary cultured hepatocytes were treated in vitro, IL-1, IL-6, conditioned medium from LPS-treated mouse macrophages, and serum from LPS-treated mouse upregulated IL-1RI mRNA expression, but LPS, TNF, and prostaglandin E(2) failed to do so, Therefore, these results suggest that the upregulation of IL-1RI mRNA in the hepatocytes by LPS administration is mediated by cytokines, especially by IL-1 and IL-6, The results also indicate that the regulation is different in different organs, and microenvirommental factors may be important.