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Elucidating Mechanisms of Airway Inflammation Following Exposure to Indoor Pollutants Such as Toner Printer-Emitted Particles (TPEs): Damps, TLRs, and the Inflammatory Loop.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Elucidating Mechanisms of Airway Inflammation Following Exposure to Indoor Pollutants Such as Toner Printer-Emitted Particles (TPEs): Damps, TLRs, and the Inflammatory Loop./
Author:	Chanetsa, Lucia.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	159 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-03, Section: B.
Contained By:	Dissertations Abstracts International82-03B.
Subject:	Toxicology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28087443
ISBN:	9798664794779

Elucidating Mechanisms of Airway Inflammation Following Exposure to Indoor Pollutants Such as Toner Printer-Emitted Particles (TPEs): Damps, TLRs, and the Inflammatory Loop.
Chanetsa, Lucia.

Elucidating Mechanisms of Airway Inflammation Following Exposure to Indoor Pollutants Such as Toner Printer-Emitted Particles (TPEs): Damps, TLRs, and the Inflammatory Loop. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 159 p.

Source: Dissertations Abstracts International, Volume: 82-03, Section: B.

Thesis (Ph.D.)--University of Massachusetts Lowell, 2020.

This item must not be sold to any third party vendors.

The objective of this research was to study the molecular mechanisms of inflammation induced by engineered nanomaterials using toner-based printer emissions (TPEs) as an example. TPEs are physicochemically complex incidental nanoparticles and engineered nanomaterials that are emitted during photocopier use. With the printing industry estimated to be worth about $4 billion and growing at an annual rate of about 5.8 %, TPEs are a growing public health concern as a source of indoor air pollution. Existing in-vitro and in-vivo studies show that TPEs cause inflammation and oxidative stress (OS). While the involvement of the NF-kB pathway in TPE induced inflammation is well-established, emerging research points towards the involvement of nanoparticle associated molecular patterns (NAMPs), damage-associated molecular patterns (DAMPs), and pattern recognition receptors such as Toll-like receptors (TLRs) in TPE induced inflammation, working together to form a circular inflammatory loop. The lung and respiratory tract are not only constantly exposed to inhaled air and by extension TPEs, but are also lined by cells that have TLRs. We hypothesized that TPEs in chronically exposed copy operators i) generate reactive oxygen species that induce OS and ii) trigger an inflammatory response by activating TLR4. We further hypothesized that the TPEs not only initiate the inflammatory response but also perpetuate it resulting in an inflammatory loop. This study investigated the involvement of TLR4 in TEP induced inflammation in-vitro using THP-1 macrophage cells. In-vivo studies were also conducted in 19 human subjects working at six copy centers to analyze the production of inflammatory biomarkers in the upper airway and systemic circulation. DAMPs, as by-products of TPE induced OS, were also analyzed.Fourteen inflammatory cytokines (Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Interleukin-1ẞ (IL-1ẞ), Interleukin-1α (IL-1α), Tumor necrosis factor-alpha (TNF-α), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Granulocyte colony-stimulating factor (G-CSF), Monocyte chemoattractant protein-1 (MCP-1), Eotaxin, Interferon- γ (INFγ), Fractalkine, Epidermal growth factor, and Vascular endothelial growth factor) were measured on a Luminex MAGPIXR 200 platform in both the nasal lavage and plasma samples collected from the copy operators on Monday pre-shift and Friday post-shift over two weeks. A sensitive, selective, and validated LC-ESI/MS/MS-based analytical method and was used to quantify a panel of frequently used urinary OS biomarkers chosen to reflect DNA/RNA damage (8OHdG, 8OHG, 5OHMeU), lipid oxidation (8-Isoprostane F2α, 4-HNE), protein and amino acid oxidation (O-Tyrosine, 3-Chlorotyrosine, and 3-Nitrotyrosine). In-vitro studies using uninduced THP-1 cells were conducted to investigate the role of TLR4 in TPE induced inflammation.Results of the in-vitro studies show that the inflammatory effects induced by TPEs are likely a culmination of multiple mechanistic pathways that include inducing cellular OS. Studies in the 19 subjects showed that urinary OS was associated with TPE exposures and exposure duration with statistically significant associations between average daily concentration and 5OHMeU, O-Tyrosine, and 8-Isoprostane. The study also showed that exposures to TPEs induce moderate upper airway inflammation and stronger systemic inflammation characterized by upregulation of IL-1β, Fractalkine, TNF-α, GM-CSF, and IFNγ. Overexpression of Fractalkine in plasma, a master regulatory cytokine involved in multiple disorders, is of particular concern and deserves special attention. The large inter-individual variability, small sample size, and the multi-factorial nature of OS complicated and weakened biomarker-exposure associations. These molecular findings, in conjunction with recently published animal inhalation studies, justify the recommendation for larger-scale epidemiological studies in these workers and consumers chronically exposed to TPEs.

ISBN: 9798664794779Subjects--Topical Terms:

556884
Toxicology.
Subjects--Index Terms:

Cell culture

Elucidating Mechanisms of Airway Inflammation Following Exposure to Indoor Pollutants Such as Toner Printer-Emitted Particles (TPEs): Damps, TLRs, and the Inflammatory Loop.
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520 $a The objective of this research was to study the molecular mechanisms of inflammation induced by engineered nanomaterials using toner-based printer emissions (TPEs) as an example. TPEs are physicochemically complex incidental nanoparticles and engineered nanomaterials that are emitted during photocopier use. With the printing industry estimated to be worth about $4 billion and growing at an annual rate of about 5.8 %, TPEs are a growing public health concern as a source of indoor air pollution. Existing in-vitro and in-vivo studies show that TPEs cause inflammation and oxidative stress (OS). While the involvement of the NF-kB pathway in TPE induced inflammation is well-established, emerging research points towards the involvement of nanoparticle associated molecular patterns (NAMPs), damage-associated molecular patterns (DAMPs), and pattern recognition receptors such as Toll-like receptors (TLRs) in TPE induced inflammation, working together to form a circular inflammatory loop. The lung and respiratory tract are not only constantly exposed to inhaled air and by extension TPEs, but are also lined by cells that have TLRs. We hypothesized that TPEs in chronically exposed copy operators i) generate reactive oxygen species that induce OS and ii) trigger an inflammatory response by activating TLR4. We further hypothesized that the TPEs not only initiate the inflammatory response but also perpetuate it resulting in an inflammatory loop. This study investigated the involvement of TLR4 in TEP induced inflammation in-vitro using THP-1 macrophage cells. In-vivo studies were also conducted in 19 human subjects working at six copy centers to analyze the production of inflammatory biomarkers in the upper airway and systemic circulation. DAMPs, as by-products of TPE induced OS, were also analyzed.Fourteen inflammatory cytokines (Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Interleukin-1ẞ (IL-1ẞ), Interleukin-1α (IL-1α), Tumor necrosis factor-alpha (TNF-α), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Granulocyte colony-stimulating factor (G-CSF), Monocyte chemoattractant protein-1 (MCP-1), Eotaxin, Interferon- γ (INFγ), Fractalkine, Epidermal growth factor, and Vascular endothelial growth factor) were measured on a Luminex MAGPIXR 200 platform in both the nasal lavage and plasma samples collected from the copy operators on Monday pre-shift and Friday post-shift over two weeks. A sensitive, selective, and validated LC-ESI/MS/MS-based analytical method and was used to quantify a panel of frequently used urinary OS biomarkers chosen to reflect DNA/RNA damage (8OHdG, 8OHG, 5OHMeU), lipid oxidation (8-Isoprostane F2α, 4-HNE), protein and amino acid oxidation (O-Tyrosine, 3-Chlorotyrosine, and 3-Nitrotyrosine). In-vitro studies using uninduced THP-1 cells were conducted to investigate the role of TLR4 in TPE induced inflammation.Results of the in-vitro studies show that the inflammatory effects induced by TPEs are likely a culmination of multiple mechanistic pathways that include inducing cellular OS. Studies in the 19 subjects showed that urinary OS was associated with TPE exposures and exposure duration with statistically significant associations between average daily concentration and 5OHMeU, O-Tyrosine, and 8-Isoprostane. The study also showed that exposures to TPEs induce moderate upper airway inflammation and stronger systemic inflammation characterized by upregulation of IL-1β, Fractalkine, TNF-α, GM-CSF, and IFNγ. Overexpression of Fractalkine in plasma, a master regulatory cytokine involved in multiple disorders, is of particular concern and deserves special attention. The large inter-individual variability, small sample size, and the multi-factorial nature of OS complicated and weakened biomarker-exposure associations. These molecular findings, in conjunction with recently published animal inhalation studies, justify the recommendation for larger-scale epidemiological studies in these workers and consumers chronically exposed to TPEs.
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