BCL-2 Mediated Apoptosis: The Role of Noxa in the Removal of Mucous Cells from the Metaplastic Human Airway Epithelium The Role of Noxa in the Removal of Mucous Cells from the Metaplastic Human Airway Epithelium

Date of Award

2009

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Demski, Leo

Keywords

Apoptosis, Noxa, Asthma, COPD, Lung

Area of Concentration

Biology

Abstract

The cytokine interferon-gamma (IFN-gamma) induces Bcl-2 mediated cell death in epithelial cells. Disruption of this process leads to mucus hypersecretions in the human airway epithelium. Apoptosis by IFN-gamma is essential for the removal of the inflammation-induced mucous cells causing the excess mucous. This buildup of mucus is the underlying cause for airflow obstruction and death caused by asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). This study demonstrates that the BH-3 only protein Noxa sensitizes human airway epithelial cells (HAECs) to IFN-gamma induced apoptosis. Noxa promotes apoptosis by interfering with transcription factor NF-kappaB. A single line of HAECs (AALEBs) transfected with Noxa siRNA exhibited reduced sensitivity to IFN-gamma associated with decreased levels of cytosolic NF-kappaB. Findings from this study suggest a novel method of NFkappaB activity inhibition by Noxa.

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