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https://zone.biblio.laurentian.ca/handle/10219/3848
Titre: | Identifying the anti-inflammatory potential of α7 nicotinic receptor silent agonists in human blood immune cells |
Auteurs: | Soto, Eduardo Carlos |
Mots clés: | Nicotinic receptors;anti-inflammatory;human blood;silent agonists;novel molecules;immune resopnse;immunology;acetylcholine;drug;flow cytometry;cytokines;signaling;surface marker;treatment |
Date publié: | 3-sep-2020 |
Abstrait: | The recent development of α7 nAChR specific molecules, referred to as silent agonists, elicit prolonged channel closing with minimal channel activation and are thought to provoke unique nAChR-dependent metabotropic signaling cascades. This study assessed the anti-inflammatory potential of several silent agonists in modulating lipopolysaccharide (LPS)-induced immune responses in human blood immune cells. Fresh whole blood from healthy volunteers was pre-treated at different time points with silent agonists followed by a 24hr LPS stimulation. Cytometric bead arrays (CBAs) were used to quantify the levels of cytokines IL-1β, IL-6, IL-10, IL-12, and TNF-α in sample supernatants. Then, BioPlex phosphoprotein kits were used to measure phosphorylation levels of various signaling pathway proteins (NF-kB, Akt, ERK1/2, STAT1, and STAT3). For this experiment, peripheral blood mononuclear cells (PBMC) and monocytes isolated from PBMCs were treated with a silent agonist during the LPS stimulation (15-120min). Finally, cell phenotyping studies were carried out in PBMC cultures treated with silent agonists and stimulated with LPS (48hrs). The markers CD14, CD16, CCR2, CD36, CD11c, and HLA-DR were studied. We report that the silent agonist pCF3 diEPP significantly downregulated the secretion of pro-inflammatory cytokines and phosphorylation of signaling proteins. We did not observe any significant findings with our cell phenotype studies. Overall, our data show that silent agonists modulate LPS-induced release of pro-inflammatory cytokines and signaling events in human peripheral blood immune cells. Silent agonists selective for α7 nAChRs may thus offer a new therapeutic strategy for the treatment of inflammatory diseases. |
URI: | https://zone.biblio.laurentian.ca/handle/10219/3848 |
Apparaît dans les collections: | Biology - Master's Theses |
Fichiers dans cet item:
Fichier | Description | Taille | Format | |
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MSc Thesis_Eduardo_Final.pdf | 2.46 MB | Adobe PDF | Parcourir/Ouvrir |
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