Rapamycin pre-treatment abrogates Tumour Necrosis Factor-alpha down-regulatory effects on LXR-alpha and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells
Electron. j. biotechnol
; Electron. j. biotechnol;14(3): 8-8, May 2011. ilus, tab
Article
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| LILACS
| ID: lil-602985
Bibliothèque responsable:
CL1.1
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-alpha (TNF-alpha) treatment reduces both LXR-alpha and PXR mRNA expression. However, pre-treatment with rapamycin, an mTOR inhibitor, followed by TNF-alpha stimulation, significantly induces LXR-alpha 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-alpha 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-alpha and PXR mRNA, after TNF-alpha treatment. Together, these observations suggest that JNK1 possibly act downstream of mTORC1 as an LXR-alpha 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-alpha and PXR as anti-inflammatory genes.
Mots clés
Texte intégral:
1
Indice:
LILACS
Sujet Principal:
Récepteurs aux stéroïdes
/
Facteur de nécrose tumorale alpha
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Sirolimus
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Récepteurs nucléaires orphelins
langue:
En
Texte intégral:
Electron. j. biotechnol
Thème du journal:
BIOTECNOLOGIA
Année:
2011
Type:
Article
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Project document