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You searched for +publisher:"University of North Carolina" +contributor:("Ezekwe, Ejiofofr"). One record found.

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University of North Carolina

1. Ezekwe, Ejiofofr. Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome.

Degree: Pharmacology, 2016, University of North Carolina

Background: Staphylococcus aureus toxin, α-hemolysin, is secreted as a soluble monomer that forms a heptameric pore in the membranes of a range of host cell types. Hemolysin binds and activates A Disintergin and Metalloprotease 10 (ADAM10) and is a well-chronicled virulence factor in staphylococcal disease. ADAM10 activity is important for toxin-mediated pathology in a number of cell types. In host monocytes, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of the pro-inflammatory cytokines (IL-1β, IL-18) and pyroptotic cell death. Human airway epithelial cells express the components of the NLRP3 inflammasome but the involvement of this signaling pathway in the cellular response to α-hemolysin is unknown. We hypothesized that both ADAM10 and NLRP3 are involved in host cellular responses to α-hemolysin in both monocytic and respiratory epithelial cells. Methods: To elucidate the role of ADAM10 and its protease activity in α-hemolysin-mediated activation of the inflammasome, we used the immortalized monocyte cells line, THP1 and U937. Cells were treated with siRNA against or chemical inhibitors of ADAM10, challenged with α-hemolysin, and NLRP3-inflammasome activation assessed by measuring secreted IL-1β, cell death, and activation of caspase-1. To test for evidence of α-hemolysin-mediated inflammasome activation in respiratory epithelial cells, we used primary human tracheobronchial epithelial (hTBE) cells and measured their secretion of IL-1β in response to hemolysin challenge. Results: Loss of ADAM10 cell surface expression led to diminished α-hemolysin-mediated activation of the NLRP3 inflammasome and cell death. ADAM10 protease activity, however, was not required for NLRP3 activation in human monocytes. hTBEs secrete mature IL-1β in response to α-hemolysin treatment, suggesting a role for the inflammasome in their response to α-hemolysin. Conclusions: This work demonstrates that ADAM10’s receptor and not its protease activity, is important for inflammasome activation by α-hemolysin in human monocytes. Preliminary evidence also suggests that the inflammasome may play a role in epithelial cell responses to α-hemolysin. Advisors/Committee Members: Ezekwe, Ejiofofr, Duncan, Joseph, Harden, T. Kendall, Ting, Jenny P.-Y., Graves, Lee, Lemon, Stanley.

Subjects/Keywords: School of Medicine; Department of Pharmacology

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APA (6th Edition):

Ezekwe, E. (2016). Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b2765954-f2a2-473f-8501-6a8bd05a8935

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Ezekwe, Ejiofofr. “Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome.” 2016. Thesis, University of North Carolina. Accessed December 05, 2020. https://cdr.lib.unc.edu/record/uuid:b2765954-f2a2-473f-8501-6a8bd05a8935.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Ezekwe, Ejiofofr. “Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome.” 2016. Web. 05 Dec 2020.

Vancouver:

Ezekwe E. Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2020 Dec 05]. Available from: https://cdr.lib.unc.edu/record/uuid:b2765954-f2a2-473f-8501-6a8bd05a8935.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ezekwe E. Cellular Mechanisms of Staphylococcus aureus α-hemolysinmediated Activation of the NLRP3 Inflammasome. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:b2765954-f2a2-473f-8501-6a8bd05a8935

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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