• Log In
  • New issue alert
  • Submit a manuscript
  • Register
  • Home
  • About
  • Editorial Board
  • Search
  • Archives
  • Current
  • Forthcoming

Share

Article Panel


Vol 14, No 3 (2011)
»Table of Contents
Reading Tools
  • About the author
  • How to cite this article
  • Indexing metadata
  • Print version
  • Look up terms
  • Finding References
  • Review policy

Related items
  • Author's work


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International.
Rapamycin pre-treatment abrogates Tumour Necrosis Factor-α down-regulatory effects on LXR-α and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells | Ng | Electronic Journal of Biotechnology
doi: 10.2225/vol14-issue3-fulltext-9
Electronic Journal of Biotechnology, Vol 14, No 3 (2011)

Rapamycin pre-treatment abrogates Tumour Necrosis Factor-α down-regulatory effects on LXR-α and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells

Di-Lin Ng, Shin-Wei Tie, Pei-Chin Ong, Wyi-Sian Lim, Tengku-Sifzizul Tengku-Muhammad, Quok-Cheong Choo, Choy-Hoong Chew



Abstract

The Liver X Receptor (LXR) and Pregnane X Receptor (PXR) are members of the nuclear receptor superfamily. Previously, they have been classified as important regulators of lipid homeostasis. However, recent studies have shown that they may be implicated in anti-inflammatory responses as well. This study shows that Tumour Necrosis Factor-α (TNF-α) treatment reduces both LXR-α and PXR mRNA expression. However, pre-treatment with rapamycin, an mTOR inhibitor, followed by TNF-α stimulation, significantly induces LXR-α and PXR mRNA expression to ~17- and ~2-fold, respectively. This suggests that mTORC1, a multi-molecular complex of which mTOR is a member, may act as a negative regulator that inhibits the induction of LXR-α and PXR as anti-inflammatory genes. It is also shown here that inhibition of JNK1 via the mTOR/Akt pathway coincides with the up-regulation of LXR-α and PXR mRNA, after TNF-α treatment. Together, these observations suggest that JNK1 possibly act downstream of mTORC1 as an LXR-α and PXR inhibitor. From the results gleaned in this study, rapamycin (and its analogues) may be used to reduce acute inflammation by promoting the induction of LXR-α and PXR as anti-inflammatory genes.




Full Text: | Full Text | Reprint PDF |

ISSN:  0717-3458

Contact: edbiotec@pucv.cl

Pontificia Universidad Católica de Valparaíso
Av. Brasil 2950, Valparaíso, Chile
Copyright © 1997- 2023 by Electronic Journal of Biotechnology