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Title: Regulation of NADPH oxidase 2 (NOX2) by adenosine monophosphate-activated kinase (AMPK) in M2-type macrophages
Authors: Raya, Elia
Advisors: Chedid, Pia
Chalhoub, Elias
Subjects: Cancer--Immunotherapy
Issue Date: 2018
The tumor microenvironment is now recognized as being an important factor for tumor progression. Tumor-Associated Macrophages (TAMs) have been shown to correlate with poor prognosis in several cancer types. Two subpopulations of TAMs coexist in the tumor microenvironment and display contradicting roles; whereas M1 have pro-inflammatory effects, M2 display anti-inflammatory functions and thus participate in tumor growth. Our preliminary results in murine immune cells have shown that Adenosine Monophosphate activated Kinase (AMPK) is involved in reactive oxygen species (ROS) production through NADPH Oxidase 2 (NOX2). In addition, NOX2 deficiency was shown to impair M2-type differentiation and number during tumor development. Therefore, our goal is to investigate if AMPK regulates NOX2 and thereby ROS production in M2-type macrophages. To do so, we first isolated human monocytes from the blood of healthy volunteers. Then, we differentiated them into M2-type macrophages. Finally, we measured the effect of AMPK activator metformin on NOX1/2 gene expression and ROS production by using qRT-PCR, and NBT assays on both differentiated M2 macrophages and human colorectal cells HCT116 cells. Consistently, metformin significantly decreased ROS production in HCT116 cells and differentiated M2 macrophages at both 1 and 3 hours. Moreover, metformin significantly reduced NOX2 expression in M2 cells corroborating NBT results. This suggests that the use of a known AMPK activator in HCT116 cells and M2 macrophages decreases NOX2 expression, which in turn decreases ROS produced by these cells thus implicating AMPK activation in this regulatory pathway.
Includes bibliographical references (p. 53-67).

Supervised by Dr. Pia Chedid and Dr. Elias Chalhoub.
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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