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dc.contributor.authorPradhan, Kishaen
dc.date.accessioned2022-01-25T09:00:07Zen
dc.date.available2022-01-25T09:00:07Zen
dc.date.issued2022-01-24en
dc.identifier.othervt_gsexam:33457en
dc.identifier.urihttp://hdl.handle.net/10919/107899en
dc.format.mediumETDen
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectmonocytesen
dc.subjectnon-resolving inflammationen
dc.subjectexhaustionen
dc.subjectTLR4 pathwayen
dc.subjectLPSen
dc.titleDose-dependent effects of endotoxin on monocyte and the underlying mechanismsen
dc.typeDissertationen
dc.contributor.departmentBiological Sciencesen
dc.description.degreeDoctor of Philosophyen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.leveldoctoralen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.disciplineBiological Sciencesen
dc.contributor.committeechairLi, Liwuen
dc.contributor.committeememberJones, Caroline N.en
dc.contributor.committeememberLiu, Dongminen
dc.contributor.committeememberLu, Changen
dc.description.abstractgeneralHealthy inflammatory response is represented by initial induction of inflammatory cells in the site of infection and pathogen clearance, followed by resolution of inflammation and damage repair. This balance between inflammation and resolution maintains immune homeostasis. Imbalances in this homeostasis can be a cause or effect of various disease conditions such as atherosclerosis and sepsis, for example. Despite rigorous research, these diseases are still prevalent and treatments are still lacking. It is essential to investigate inflammatory responses at a cellular level and understand how an immune cell responds to a given pathogen. Depending upon the intensity, dose and duration of a pathogen can dictate immune cell functions. Recent discoveries, including the research in our lab have reported that super low dose bacterial endotoxin exacerbates atherosclerosis. Mouse monocytes (innate immune cells) treated with super low dose endotoxin continuously induce mild but sustained inflammatory molecules but are unable to exhibit resolving mediators to dampen the inflammation and hence, monocyte homeostasis is disrupted. Homeostatic imbalance is also in seen in sepsis, when monocytes exposed to high dose bacterial endotoxin. Due to a repetitive exposure to high dose endotoxin, monocytes are unable to respond accurately, where they simultaneously exhibit inflammatory and anti-inflammatory mediators but in a dysregulated manner.en


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