Calantone et al 2022 Commun Biol Source Data Open Access (recommended)

Source data uploaded for the work in press at time of upload: "mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses."

Keyword: metabolism
monocytes
immunology
Rights: All rights reserved
Contributor: D'Aquila, Richard Thomas
Calantone, Nina Alexandra
Abstract: Translocated lipopolysaccharide (LPS) activates monocytes via TLR4 and is hypothesized to increase cardiovascular disease risk in persons living with HIV. We tested whether mTOR activity supports LPS-stimulated monocyte production of pro-inflammatory cytokines and tissue factor (TF), as it propels the inflammatory response in several immune cell types besides monocytes. However, multi-omics analyses here demonstrate that mTOR activates a metabolic pathway that limits abundance of these gene products in monocytes. Treatment of primary human monocytes with catalytic mTOR inhibitors (mTORi) increased LPS-induced polyfunctional responses, including production of IL-1, IL-6 and the pro-coagulant, TF. NF-B-driven transcriptional activity is enhanced with LPS stimulation after mTORi treatment to increase expression of F3 (TF). Moreover, intracellular NAD+ availability is restricted due to decreased salvage pathway synthesis. These results document mTOR-mediated restraint of the LPS-induced transcriptional response in monocytes and a metabolic mechanism informing strategies to reverse enhanced risk of coagulopathy in pro-inflammatory states.
Publisher: DigitalHub. Galter Health Sciences Library & Learning Center
Language: English
Subject: MESH: Metabolism
Monocytes
Allergy and Immunology
MTOR Inhibitors
Total Items: 21
Size: 24.7 MB

Not a member of any collections

Descriptions

Actions

Items in this Collection