Please use this identifier to cite or link to this item: https://zone.biblio.laurentian.ca/handle/10219/3848
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dc.contributor.authorSoto, Eduardo Carlos-
dc.date.accessioned2022-04-08T15:24:00Z-
dc.date.available2022-04-08T15:24:00Z-
dc.date.issued2020-09-03-
dc.identifier.urihttps://zone.biblio.laurentian.ca/handle/10219/3848-
dc.description.abstractThe 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.en_US
dc.language.isoenen_US
dc.subjectNicotinic receptorsen_US
dc.subjectanti-inflammatoryen_US
dc.subjecthuman blooden_US
dc.subjectsilent agonistsen_US
dc.subjectnovel moleculesen_US
dc.subjectimmune resopnseen_US
dc.subjectimmunologyen_US
dc.subjectacetylcholineen_US
dc.subjectdrugen_US
dc.subjectflow cytometryen_US
dc.subjectcytokinesen_US
dc.subjectsignalingen_US
dc.subjectsurface markeren_US
dc.subjecttreatmenten_US
dc.titleIdentifying the anti-inflammatory potential of α7 nicotinic receptor silent agonists in human blood immune cellsen_US
dc.typeThesisen_US
dc.description.degreeMaster of Science (MSc) in Biologyen_US
dc.publisher.grantorLaurentian University of Sudburyen_US
Appears in Collections:Biology - Master's Theses

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