Journal article
Mesenchymal stromal cells can block palmitate training of macrophages via cyclooxygenase-2 and interleukin-1 receptor antagonist
Cytotherapy (Oxford, England), Vol.27(2), pp.169-180
02/2025
DOI: 10.1016/j.jcyt.2024.10.011
PMID: 39580716
Abstract
•Palmitate drives trained immunity in human macrophages dependent on epigenetic remodelling•Palmitate training promotes an M2 phenotypic switch with CD206 expression•MSCs suppress palmitate training pro-inflammatory cytokine production by macrophages•MSCs do not alter palmitate training induced M2 phenotypic switch•MSCs block palmitate training of macrophages via COX-2 and IL-1Ra
Innate training of macrophages can be beneficial for the clearance of pathogens. However, for certain chronic conditions innate training can have detrimental effects due to an excessive production of pro-inflammatory cytokines. Obesity is a condition that is associated with a range of increased pro-inflammatory training stimuli including the free fatty acid palmitate. Mesenchymal stromal cells (MSCs) are powerful immunomodulators and known to suppress inflammatory macrophages via a range of soluble factors. We show that palmitate training of murine bone-marrow derived macrophages and human monocyte-derived macrophages (MDMs) results in an increased production of TNFα and IL-6 upon stimulation with LPS and is associated with epigenetic remodelling. Palmitate training led to metabolic changes, however, MSCs did not alter the metabolic profile of human MDMs. Using a transwell system, we demonstrated that human bone marrow MSCs block palmitate training in both murine and human macrophages suggesting the involvement of secreted factors. MSC disruption of the training process occurs through more than one pathway. Suppression of palmitate enhanced TNFα production is associated with COX-2 activity in MSCs, while secretion of IL-1Ra by MSCs is required to suppress palmitate enhanced IL-6 production in MDMs.
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Details
- Title: Subtitle
- Mesenchymal stromal cells can block palmitate training of macrophages via cyclooxygenase-2 and interleukin-1 receptor antagonist
- Creators
- Laura M. Bitterlich - National University of Ireland, MaynoothCourteney Tunstead - National University of Ireland, MaynoothAndrew E. Hogan - National University of Ireland, MaynoothJames A. Ankrum - University of Iowa Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, 52242, USAKaren English - National University of Ireland, Maynooth
- Resource Type
- Journal article
- Publication Details
- Cytotherapy (Oxford, England), Vol.27(2), pp.169-180
- DOI
- 10.1016/j.jcyt.2024.10.011
- PMID
- 39580716
- NLM abbreviation
- Cytotherapy
- ISSN
- 1465-3249
- eISSN
- 1477-2566
- Publisher
- Elsevier Inc
- Grant note
- John & Pat Hume doctoral awards of Maynooth UniversityMaynooth University Department of Biology Contingency Research FundScience Foundation Ireland (SFI): 16/RI/3399
This publication has emanated from research supported by the John & Pat Hume doctoral awards of Maynooth University, the Maynooth University Department of Biology Contingency Research Fund and in part by a research grant from Science Foundation Ireland (SFI) under Grant Number 16/RI/3399.
- Language
- English
- Electronic publication date
- 10/2024
- Date published
- 02/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984746193902771
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