During wintertime temperature inversion episodes the concentrations of particulate air pollution, also defined as particulate matter (PM), in Utah’s Cache Valley have often been highest in the nation, with concentrations surpassing more populated and industrial areas. This has attracted much local and national attention to the area and its pollution. The Cache Valley has recently been declared to be in non-attainment of provisions of Federal law bringing to bear Federal regulatory attention as well. While there is epidemiological evidence indicating that PM is detrimental to public health, there is much less information indicating by which biological and molecular mechanisms PM can exert harm. This study was undertaken to better understand the mechanisms by which ambient PM collected in the Cache Valley can be harmful to human lung cells. Cache Valley PM was found to be mildly cytotoxic only at concentrations that were much greater than physiologically achievable, and such concentrations were difficult to obtain with the limited amounts of captured ambient PM. The limited cytotoxicity was despite apparent PM-induced pro-apoptotic signaling such as caspase-3 upregulation, and activation of caspase-12 and calpain. Cache Valley PM was found to be stressful to cells, triggering endoplasmic reticulum stress and the unfolded protein response. Cache Valley PM was also found to be inflammogenic leading to activation of pro-inflammatory transcription factors, increases in the release of pro-inflammatory cytokines and chemokines, as well as the upregulation of the activating receptors of these cytokines. The proinflammatory effects and absence of apoptosis, despite pro-apoptotic signaling of the Cache Valley PM on human lung cells appeared to stem from increased activation of the central pro-growth protein Akt with subsequent inactivation of the tumor suppressor P-TEN. These findings have indicated novel mechanisms of PM-related cellular stress and inflammation contributing needed information on what may be underlying mechanisms of PM associcated illnesses.
| Identifer | oai:union.ndltd.org:UTAHS/oai:digitalcommons.usu.edu:etd-2326 |
| Date | 01 May 2012 |
| Creators | Watterson, Todd L. |
| Publisher | DigitalCommons@USU |
| Source Sets | Utah State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Graduate Theses and Dissertations |
| Rights | Copyright for this work is held by the author. Transmission or reproduction of materials protected by copyright beyond that allowed by fair use requires the written permission of the copyright owners. Works not in the public domain cannot be commercially exploited without permission of the copyright owner. Responsibility for any use rests exclusively with the user. For more information contact Andrew Wesolek (andrew.wesolek@usu.edu). |
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