Please use this identifier to cite or link to this item: http://localhost:8080/xmlui/handle/123456789/934
Title: Inflammation-induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation
Authors: Banerjee, D.
Sinha, A.
Saikia, S.
Gogoi, B.
Rathore, B.
Das, A.S.
Pal, D.
Buragohain, A.K.
Dasgupta, S.
Keywords: Akt phosphorylation
Inflammation
Macrophage foam cell
mTORC2
TLR4 signaling
Issue Date: 30-Aug-2018
Abstract: The transformation of macrophages into lipid-loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression, and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation-induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation.
URI: http://localhost:8080/xmlui/handle/123456789/934
Appears in Collections:Year-2018

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