Blockade of mTORC1 via Rapamycin Suppresses 27-Hydroxycholestrol-Induced Inflammatory Responses

Atherosclerosis is characterized by the deposition and accumulation of extracellular cholesterol and inflammatory cells in the arterial blood vessel walls, and 27-hydroxycholesterol (27OHChol) is the most abundant cholesterol metabolite. 27OHChol is an oxysterol that induces immune responses, includ...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of molecular sciences Vol. 25; no. 19; p. 10381
Main Authors:	Kang, Nakyung, Kim, Jaesung, Kwon, Munju, Son, Yonghae, Eo, Seong-Kug, Baryawno, Ninib, Kim, Byoung Soo, Yoon, Sik, Oh, Sae-Ock, Lee, Dongjun, Kim, Koanhoi
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-10-2024 MDPI
Subjects:	27-hydroxycholesterol Atherosclerosis Atherosclerosis - drug therapy Atherosclerosis - metabolism Atherosclerosis - pathology Cell adhesion & migration Cell growth Chemokine CCL2 - metabolism Chemokines Cholesterol Cytokines Development and progression Drug therapy Health aspects Humans Hydroxycholesterols - pharmacology Immune system Inflammation Inflammation - drug therapy Inflammation - metabolism Inflammation - pathology Lipopolysaccharide Receptors - metabolism Macrophages - drug effects Macrophages - metabolism Mechanistic Target of Rapamycin Complex 1 - metabolism Monocytes - drug effects Monocytes - metabolism monocytic cells mTOR Phosphorylation Phosphorylation - drug effects Physiological aspects Proteins Rapamycin Ribonucleic acid RNA Signal Transduction - drug effects Sirolimus - pharmacology Smooth muscle THP-1 Cells South Korea monocytic cells mTOR 27-hydroxycholesterol inflammation rapamycin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Atherosclerosis is characterized by the deposition and accumulation of extracellular cholesterol and inflammatory cells in the arterial blood vessel walls, and 27-hydroxycholesterol (27OHChol) is the most abundant cholesterol metabolite. 27OHChol is an oxysterol that induces immune responses, including immune cell activation and chemokine secretion, although the underlying mechanisms are not fully understood. In this study, we investigated the roles of the mechanistic target of rapamycin (mTOR) in 27HChol-induced inflammation using rapamycin. Treating monocytic cells with rapamycin effectively reduced the expression of CCL2 and CD14, which was involved with the increased immune response by 27OHChol. Rapamycin also suppressed the phosphorylation of S6 and 4EBP1, which are downstream of mTORC1. Additionally, it also alleviates the increase in differentiation markers into macrophage. These results suggest that 27OHChol induces inflammation by activating the mTORC1 signaling pathway, and rapamycin may be useful for the treatment of atherosclerosis-related inflammation involving 27OHchol.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms251910381