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TLR7 Expression Is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis.
- Source :
-
Cells [Cells] 2020 Jul 16; Vol. 9 (7). Date of Electronic Publication: 2020 Jul 16. - Publication Year :
- 2020
-
Abstract
- Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR7) in CAVS, especially in relation to macrophage subtype. Human aortic valves were used for mRNA expression analysis, immunofluorescence staining, or ex vivo tissue assays. Response to TLR7 agonist in primary macrophages and valvular interstitial cells (VICs) were investigated in vitro. In the aortic valve, TLR7 correlated with M2 macrophage markers on mRNA levels. Expression was higher in the calcified part compared with the intermediate and healthy parts. TLR7 <superscript>+</superscript> cells were co-stained with M2-type macrophage receptors CD163 and CD206. Ex vivo stimulation of valve tissue with the TLR7 ligand imiquimod significantly increased secretion of IL-10, TNF-α, and GM-CSF. Primary macrophages responded to imiquimod with increased secretion of IL-10 while isolated VICs did not respond. In summary, in human aortic valves TLR7 expression is associated with M2 macrophages markers. Ex vivo tissue challenge with TLR7 ligand led to secretion of immunomodulatory cytokine IL-10. These results connect TLR7 activation in CAVS to reduced inflammation and improved clearance.
- Subjects :
- Aortic Valve metabolism
Biomarkers metabolism
Cells, Cultured
Cytokines metabolism
Humans
Imiquimod pharmacology
Ligands
T-Lymphocytes drug effects
T-Lymphocytes metabolism
Toll-Like Receptor 7 agonists
Aortic Valve pathology
Aortic Valve Stenosis metabolism
Calcinosis metabolism
Macrophages metabolism
Toll-Like Receptor 7 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 32708790
- Full Text :
- https://doi.org/10.3390/cells9071710