3 research outputs found
Rapamycin pre-treatment abrogates Tumour Necrosis Factor-\u3b1 down-regulatory effects on LXR-\u3b1 and PXR mRNA expression via inhibition of c-Jun N-terminal kinase 1 activation in HepG2 cells
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-\u3b1
(TNF-\u3b1) treatment reduces both LXR-\u3b1 and PXR mRNA expression.
However, pre-treatment with rapamycin, an mTOR inhibitor, followed by
TNF-\u3b1 stimulation, significantly induces LXR-\u3b1 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-\u3b1 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-\u3b1 and PXR mRNA, after TNF-\u3b1 treatment. Together, these
observations suggest that JNK1 possibly act downstream of mTORC1 as an
LXR-\u3b1 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-\u3b1 and PXR as anti-inflammatory
genes
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
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