ENDOTOXIN-INDUCED UP-REGULATION OF TYPE-I INTERLEUKIN-1 RECEPTOR MESSENGER-RNA EXPRESSION IN HEPATOCYTES OF MICE - ROLE OF CYTOKINES

Interleukin-1 (IL-1) signal is transduced through the type I IL-1 rece ptor (IL-1RI). Although regulation of IL-1R expression has been extens ively studied in vitro, little is known about it in vivo. By using RT- PCR analysis, we investigated the regulation of the IL-1RI mRNA expres sion level in various organs of mice at 2, 6, and 24 h following lipop olysaccharide (LPS) administration, IL-1RI mRNA expression in response to LPS appeared to be different in various organs, As a marked and su stained increase of IL-1RI mRNA expression in the liver was observed, we investigated the mechanism of the upregulation, IL-1, IL-6, and tum or necrosis factor (TNF) all increased the mRNA expression in the live r when administrated in vivo, In situ hybridization revealed that upre gulation of IL-1R mRNA was observed in parenchymal liver cells (hepato cytes) in response to LPS administration, When primary cultured hepato cytes were treated in vitro, IL-1, IL-6, conditioned medium from LPS-t reated mouse macrophages, and serum from LPS-treated mouse upregulated IL-1RI mRNA expression, but LPS, TNF, and prostaglandin E(2) failed t o do so, Therefore, these results suggest that the upregulation of IL- 1RI mRNA in the hepatocytes by LPS administration is mediated by cytok ines, especially by IL-1 and IL-6, The results also indicate that the regulation is different in different organs, and microenvirommental fa ctors may be important.