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Electronic Journal of Biotechnology
Universidad Católica de Valparaíso
ISSN: 0717-3458
Vol. 14, No. 3, 2011
Bioline Code: ej11031
Full paper language: English
Document type: Review Article
Document available free of charge

Electronic Journal of Biotechnology, Vol. 14, No. 3, 2011

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

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.

Keywords
Akt, c-Jun, homeostasis, inflammation, MKK7, transcription factor

 
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