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Mesenchymal stromal cells regulate THP-1-differentiated macrophage cytokine production by activating Akt/mammalian target of rapamycin complex 1 pathway
Cited 1 time in
Web of Science
Cited 2 time in Scopus
- Authors
- Issue Date
- 2023-08
- Publisher
- Taylor & Francis
- Citation
- Cytotherapy, Vol.25 No.8, pp.858-865
- Abstract
- Background aims: The Akt/mammalian target of rapamycin (mTOR) pathway in macrophages converges inflammatory and metabolic signals from multiple receptors to regulate a cell's survival, metabolism and activation. Although mesenchymal stromal cells (MSCs) are well known to modulate macrophage activation, the effects of MSCs on the Akt/mTOR pathway in macrophages have not been elucidated.Methods: We herein investigated whether MSCs affect the Akt/mTOR complex 1 (mTORC1) pathway to regulate macrophage polarization.Results: Results showed that human bone marrow-derived MSCs induced activation of Akt and its downstream mTORC1 signaling in THP-1-differentiated macrophages in a p62/sequestosome 1-independent manner. Inhibition of Akt or mTORC1 attenuated the effects of MSCs on the suppression of tumor necrosis factor-a and interleukin-12 production and the promotion of interleukin-10 and tumor growth factor-b1 in macrophages stimulated by lipopolysaccharide/ATP. Conversely, activation of Akt or mTORC1 reproduced and potentiated MSC effects on macrophage cytokine production. MSCs with cyclooxygenase-2 knockdown, however, failed to activate the Akt/mTORC1 signaling in macrophages and were less effective in the modulation of macrophage cytokine production than control MSCs.Conclusions: These data demonstrate that MSCs control THP-1-differentiated macrophage activation at least partly through upregulation of the Akt/mTORC1 signaling in a cyclooxygenase-2-dependent manner.& COPY; 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
- ISSN
- 1465-3249
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