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 E2 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 microenvironmental factors may be important.
Ito
A
A
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Takii
T
T
Soji
T
T
Onozaki
K
K
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / 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*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha