Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Hepatol. 2004 Apr;40(4):616-23.

Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes.

Author information

  • 1Department of Surgery, Kansai Medical University, Osaka 570-8506, Japan.

Abstract

BACKGROUND/AIMS:

Nuclear translocation and DNA binding of NF-kappaB is essential, as interleukin-1beta (IL-1beta) stimulates the induction of inducible nitric oxide synthase (iNOS) gene expression in hepatocytes. However, recent evidence indicates that the activation of NF-kappaB is not sufficient to induce the NF-kappaB-dependent transcription, and the existence of a second signaling is postulated.

METHODS:

Primary cultured hepatocytes were treated with IL-1beta, and the expression of iNOS and type 1 IL-1 receptor (IL-1R1) was analyzed in the presence of antisense of IL-1R1, phosphatidylinositol 3-kinase (PI3K) inhibitor, proteasome inhibitor and hypoxia. Moreover, the activities of Akt and NF-kappaB were recorded and the cotransfection was carried out.

RESULTS:

Antisense experiment revealed that IL-1R1 was required for iNOS transcription. IL-1beta markedly stimulated the induction of IL-1R1, which preceded the induction of iNOS. The IL-1R1 induction was found to be PI3K/Akt-dependent but NF-kappaB-independent. The up-regulation of IL-1R1 was associated with the second activation of Akt, which accelerated the phosphorylation of NF-kappaB p65 subunit. Cotransfection experiments revealed that Akt increased the transcriptional activity of iNOS gene promoter.

CONCLUSIONS:

These results indicate that the up-regulation of IL-1R1 in concert with the activation of NF-kappaB is required for the transcriptional activation of iNOS gene.

PMID:
15030977
[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk