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Date of Award

2018

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

Abstract

Following events of cellular and tissue damage due to infection, injury, and metabolic stress, inflammation acts to naturally protect the body against further negative effects (Kushner, 2017; Munn, 2017; Kondylis et al., 2017). One important immune cell type involved in inflammation is the macrophage. Macrophages are capable of initiating the inflammatory response through their recognition of damage-associated molecular patterns (DAMPs) released by necrotic cells and pathogen-associated molecular patterns (PAMPs) found on pathogens. This initiation involves the release of cytokines and chemokines and the subsequent recruitment of immune effector cells to the affected area (Gordon, 2002; Martin, 2016; Komai et al., 2017).

My studies have focused on a refined analog of JG-03-14 called NT-07-16, which has an additional methoxy group at the 2-position of the phenyl ring (Fig. 1). The additional methoxy group on NT-07-16 increases its water solubility and enhances its ability to interact with the target site on the tubulin protein (Da et al., 2012; Rohena et al., 2016). We sought to further understand the effects of NT-07-16 on macrophage pro-inflammatory activity, therefore we used the RAW264.7 mouse macrophage cell line. Prior to activating the macrophages with LPS, we exposed the cells to NT-07-16. We then measured production of pro-inflammatory cytokines. We utilized fluorescence microscopy to assess the translocation of NF-κB into the nucleus. Finally, we performed studies of the phosphorylation of IκB-α and also the interaction between NF-κB with microtubules to understand how depolymerization of the microtubules by NT-07-16 may alter NF-κB translocation, a relationship which has been studied but is yet to be elucidated (Manié et al., 1993; Rosette & Karin, 1995; Crépieux et al.,1997; Rao et al., 1997; Spencer et al., 1999; Jackman et al., 2009; Shrum et al., 2009; Rai et al., 2015).

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