Estrogen and Progesterone enhance Neisseria gonorrhoeae Transmigration across a Polarized Monolayer via a Mechanism that Hijacks EGFR

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dc.contributor.advisorSong, Wenxiaen_US
dc.contributor.authorEdwards, Vonetta Lisaen_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2012-10-11T06:09:28Z
dc.date.available2012-10-11T06:09:28Z
dc.date.issued2012en_US
dc.description.abstractGonorrhea, a common sexually transmitted infection, is caused by the gram-negative bacterium <italic>Neisseria gonorrhoeae</italic>. In the female reproductive tract, gonococci (GC) initiate infection at the apical surface of columnar endocervical epithelial cells. These cells provide a physical barrier against mucosal pathogens by forming continuous apical junctional complexes between neighboring cells. This study examines the interaction of GC with polarized epithelial cells. We show that viable, but not gentamicin killed, GC preferentially localize at the apical side of the cell-cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84, respectively. In GC infected epithelial cells, continuous apical junctional complexes are disrupted, and the junction-associated protein &beta;-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites. However, GC inoculation does not change the overall cellular level of junctional proteins. This redistribution of junctional proteins is associated with a decrease in the apical junction's barrier function against the lateral movement between the apical and basolateral membranes, but not against the permeability through the paracellular space. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and &beta;-catenin, while inhibition of EGFR kinase significantly reduces both GC-induced &beta;-catenin redistribution and GC transmigration. These results suggest a relationship between junction protein redistribution from the plasma membrane with the resultant weakening of the junctional complex, and an increase in the ability of GC to transmigrate. The presence of the female sex hormones estrogen and progesterone, lead to an increased degree of disruption of the junctional complex and enhance GC transmigration across the monolayer. Therefore, GC are capable of weakening the apical junction and the polarity of epithelial cells via activating EGFR, which facilitates GC transmigration across the epithelium.en_US
dc.identifier.urihttp://hdl.handle.net/1903/13234
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pqcontrolledMicrobiologyen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pquncontrolledApical junctionen_US
dc.subject.pquncontrolledEGFRen_US
dc.subject.pquncontrolledEstrogenen_US
dc.subject.pquncontrolledNeisseria gonorrhoeaeen_US
dc.subject.pquncontrolledProgesteroneen_US
dc.subject.pquncontrolledTransmigrationen_US
dc.titleEstrogen and Progesterone enhance Neisseria gonorrhoeae Transmigration across a Polarized Monolayer via a Mechanism that Hijacks EGFRen_US
dc.typeDissertationen_US

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