Divergent regulation of inflammatory cytokines by mTORC1 in THP-1–derived macrophages and intestinal epithelial Caco-2 cells

Harleen Kaur, Anjeza Erickson, Régis Moreau

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Aims: The sustained activation of intestinal mechanistic target of rapamycin complex 1 (mTORC1) brought about by repeated mucosal insult or injury has been linked to escalation of gut inflammatory response, which may progress to damage the epithelium if not controlled. This study investigated the role of mTORC1 in the response of macrophage and enterocyte to inflammatory stimuli. Materials and methods: We genetically manipulated human THP-1 monocytes and epithelial intestinal Caco-2 cells to generate stable cell lines with baseline, low or high mTORC1 kinase activity. The effects of THP-1 macrophage secretions onto Caco-2 cells were investigated by means of conditioned media transfer experiments. Key findings: The priming of mTORC1 for activation promoted lipopolysaccharide (LPS)-mediated THP-1 macrophage immune response as evidenced by the stimulation of inflammatory mediators (TNFα, IL-6, IL-8, IL-1β and IL-10). The treatment of THP-1 macrophages with LPS more than the manipulated level of mTORC1 activity of macrophages determined whether cytokine gene expression was induced in Caco-2 cells. LPS carry over was not responsible for the stimulation of Caco-2 cells' cytokine response. Knocking down Raptor in Caco-2 cells or treating Caco-2 cells with rapamycin enhanced Caco-2 TNFα gene expression revealing the anti-inflammatory role of a functional mTORC1 in intestinal epithelial cells exposed to macrophage-derived pro-inflammatory stimuli. Significance: Taken together, mTORC1 differentially impacts the immune responses of THP-1–derived macrophages and Caco-2 epithelial cells when placed in a pro-inflammatory microenvironment.

Original languageEnglish (US)
Article number119920
JournalLife Sciences
StatePublished - Nov 1 2021


  • Cell differentiation
  • Endotoxin
  • Gut innate immunity
  • Interleukin
  • Rapamycin
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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