Open Access Theses and Dissertations

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1. Buzzy, Christina Antonopoulos. NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES.

Degree: PhD, Pathology, 2015, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1417718855 

Dysregulated IL-1ß production has been implicated in a host of disease settings, ranging from autoinflammatory syndromes to diabetes and Alzheimer’s disease. The first-identified interleukin-converting enzyme or `ICE’ was caspase-1. The assembly of cytosolic, multi-protein complexes called inflammasomes canonically triggers the activation of caspase-1. Following proximity-induced autocatalysis of procaspase-1 dimers, activated caspase-1 molecules proteolytically catalyze the conversion of the pro- inflammatory cytokines, proIL-1ß and proIL-18, into their mature cytokines, IL-1ß and IL-18. As will be discussed in the following chapters, the coordination of IL-1ß cytokine generation is under the regulation of the individual proteins which comprise the particular cytosolic, multi-protein complex.Caspase-8 has recently emerged as an alternative ICE in response to microbially- induced inflammation for the generation of mature IL-1ß and IL-18. My dissertation studies contribute to this rapidly growing field in multiple unique facets. First, in the genetic absence of caspase-1, caspase-8 is recruited to an ASC-containing platform for IL-1ß processing in response to nigericin in dendritic cells (DCs). Besides acting as a direct IL-1ß convertase, caspase-8 also regulates the activation of caspase-1 induced by nigericin in LPS-primed control DCs, adding an additional layer of complexity to IL-1ß regulation. In the context of anti-cancer treatment, the commonly used pro-apoptotic chemotherapeutic drug, doxorubicin (Dox), induces a non-canonical IL-1ß processing platform, consisting of RIP1/FADD/caspase-8 and is driven by the downregulation of the cellular inhibitor of apoptosis protein 1 (cIAP1). Enzymatically active caspase-8 then promotes IL-1ß maturation within this specific ripoptosome complex. Of particular interest is how this inflammatory signaling pathway may contribute to cancer pathogenesis or amelioration during treatment with Dox.My data additionally demonstrate the intertwined nature of inflammatory and cell death signaling pathways. The activity of IL-1ß convertases, caspase-1 and caspase-8, dictates which mode of cell death a TLR4-primed macrophage/DC will undergo and is highly stimulus-dependent. Consequently, IL-1ß signaling is closely associated with pyroptosis when a caspase-1 platform is engaged and apoptotosis when a caspase-8 platform is engaged. Herein this thesis, I discriminate between caspase-1- and caspase-8- based signaling pathways in murine dendritic cells and macrophages for the proteolytic maturation of IL-1ß. Advisors/Committee Members: Dubyak, George (Advisor), Pearlman, Eric (Committee Chair).

Subjects/Keywords: Immunology; Biology; caspase-8; IL-1b processing; pro-apoptotic chemotherapeuitc drugs; NLRP3; inflammasome

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Buzzy, C. A. (2015). NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1417718855

Chicago Manual of Style (16th Edition):

Buzzy, Christina Antonopoulos. “NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES.” 2015. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed March 04, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1417718855.

MLA Handbook (7th Edition):

Buzzy, Christina Antonopoulos. “NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES.” 2015. Web. 04 Mar 2021.

Vancouver:

Buzzy CA. NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2015. [cited 2021 Mar 04]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1417718855.

Council of Science Editors:

Buzzy CA. NON-CANONICAL IL-1ß PROCESSING VIA CASPASE-8 IN MURINE DENDRITIC CELLS AND MACROPHAGES. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1417718855


IUPUI

2. Howe, Christopher Ryan. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.

Degree: 2020, IUPUI

URL: http://hdl.handle.net/1805/22885 

Indiana University-Purdue University Indianapolis (IUPUI) Advisors/Committee Members: Johnson, Steven M., Hoang, Quyen Q., Meroueh, Samy O..

Subjects/Keywords: Pro-Drugs; GroEL/ES; Chaperone Proteins; Nitrofurans; Hydroxyquinolines; Nitroreductases; Inhibitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Howe, C. R. (2020). Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/22885

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):

Howe, Christopher Ryan. “Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.” 2020. Thesis, IUPUI. Accessed March 04, 2021. http://hdl.handle.net/1805/22885.

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

MLA Handbook (7th Edition):

Howe, Christopher Ryan. “Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli.” 2020. Web. 04 Mar 2021.

Vancouver:

Howe CR. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. [Internet] [Thesis]. IUPUI; 2020. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1805/22885.

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

Council of Science Editors:

Howe CR. Analogues of Nitrofuran Antibiotics are Potent GroEL/ES Pro-drug Inhibitors with Efficacy against Enterococcus Faecium, Staphylococcus Aureus, and Escherichia Coli. [Thesis]. IUPUI; 2020. Available from: http://hdl.handle.net/1805/22885

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

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