Roles of Endothelial Toll-like Receptor (TLR) 4 in Neutrophil Recruitment During Experimental Colitis

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atmire.migration.oldid5256
dc.contributor.advisorWaterhouse, Christopher Curns
dc.contributor.authorWang, Tie
dc.contributor.committeememberXue, Yingwei
dc.contributor.committeememberMacNaughton, Wallace Keith
dc.contributor.committeememberMcKay, Derek Mark
dc.contributor.committeememberSun, Wenjing
dc.date.accessioned2017-01-17T23:13:28Z
dc.date.available2017-01-17T23:13:28Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractThe innate immune system uses pattern recognition receptors (PRRs) encoded by germline genes of the host to detect danger signals from damaged tissues as well as conserved microbial “molecular patterns” called damage- or pathogen-associated molecular patterns (DAMPs or PAMPs). PRRs are essential for the initiation of immune responses. Among PRRs, Toll-like Receptor (TLR) 4 has gained a great deal of attention, as it is the first discovered PRR, and it is the receptor for lipopolysaccharide (LPS, a major cell wall component of Gram-negative bacteria). It has been demonstrated that TLR4 has many roles in the pathogenesis of inflammatory bowel diseases (IBD) and experimental colitis. However, the functions of endothelial TLR4 remain unclear. In this thesis, we hypothesized that endothelial TLR4 provokes neutrophil recruitment in the colon during experimental colitis. Endothelial TLR4 is upregulated during dextran sulfate sodium (DSS)-induced colitis, in part by tumor necrosis factor (TNF)-α. The upregulation of endothelial TLR4 occurs prior to neutrophil recruitment in DSS colitis. Loss of endothelial TLR4 attenuates the histological damage in DSS-induced colitis. Mice lacking endothelial TLR4 have fewer colonic neutrophils during DSS colitis. Mice with a specific deletion of endothelial TLR4 have a decreased number of adherent neutrophils in the microcirculation of their colon upon DSS challenge. NanoString nCounter CodeSet analysis showed endothelial intercellular adhesion molecule (ICAM) 2 has lower expression in mice lacking endothelial TLR4, measured by immunofluorescence and flow cytometry. In vitro cultured endothelial cells respond to LPS challenge to increase the expression of ICAM2. Blocking of ICAM2 also inhibits neutrophil adhesion in DSS colitis. In conclusion, endothelial TLR4 is an active player in experimental colitis and mediates neutrophil recruitment.en_US
dc.identifier.citationWang, T. (2017). Roles of Endothelial Toll-like Receptor (TLR) 4 in Neutrophil Recruitment During Experimental Colitis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27690en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27690
dc.identifier.urihttp://hdl.handle.net/11023/3571
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectImmunology
dc.subject.otherToll-like receptor 4
dc.subject.otherEndothelial Cells
dc.subject.otherexperimental colitis
dc.subject.otherneutrophil recruitment
dc.subject.otherinflammatory bowel diseases
dc.titleRoles of Endothelial Toll-like Receptor (TLR) 4 in Neutrophil Recruitment During Experimental Colitis
dc.typedoctoral thesis
thesis.degree.disciplineGastrointestinal Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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