MTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.

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-1β, IL-6, and the pro-coagulant, TF. NF-κB-driven transcriptional activity is enhanced with LPS stimulation after mTORi treatment

SUBMITTER: Lund NC 

PROVIDER: S-EPMC9412771 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature