Date of Graduation

Spring 2023

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Christopher Lupfer

Abstract

A cell cycle's progression has a significant role in the development of a disease. All the signaling pathways and inflammatory reactions are maintained in a healthy mode if cell cycle checkpoints are precisely regulated and kept in homeostasis. AIM2 inflammasome is a cytoplasmic double-stranded DNA sensor. Upon activation, it elicits an inflammatory reaction with the release of pro-inflammatory cytokines such as IL-1β and IL-18 and they are cleaved by the proteases, Caspase-1 from their inactive form. Also, the AIM2 inflammasome helps in regulating cell division and inhibits cell proliferation; thus, leading to a cell death called pyroptosis. Here, I examined the effects of inhibiting the cell cycle on the AIM2 inflammasome. Furthermore, I investigated whether AIM2 gets inactivated or shut down during mitosis. By using immortalized murine macrophages and treating these cells with LPS, DNA, and etoposide, I found that there was a change in AIM2 gene expression. However, there was no significant change in AIM2 protein level or IL-1β levels. My data indicates that mRNA expression is not solely responsible for controlling AIM2 expression and inflammasome activation but also there might be some internal activation such as phosphorylation or post-translational modifications going on.

Keywords

inflammasome, AIM2, caspase-1, cytokine, etoposide, IL-1β, IL-18, LPS

Subject Categories

Immunology and Infectious Disease

Copyright

© Ashok Kumar Dubey

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