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Date of Award

2020

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Dr. Shannon Jones

Abstract

Over three billion people burn wood and other biomass fuels as their primary source of heating and cooking. However, long-term exposure to wood smoke leads to chronic immune activation. The aim of this project was to evaluate the pathways that mediate wood smoke induced inflammation, and the anti-inflammatory properties of the compound paeonol (2'-Hydroxy-4'-methoxyacetophenone) as a potential treatment. Paeonol is derived from the root of two Chinese species of peony plant, and has been shown to have anti-inflammatory, pain relieving, and anti-tumor properties through suppression of the NFĸB pathway. However, its effects on lung cell inflammation and macrophage activity in vitro is not well understood. THP-1 human monocytes were cultured for 24 hours and treated with varying concentrations of paeonol, from 10-200 μM, then challenged with LPS as a control (known to activate NFĸB), solubilized wood smoke, or acrolein, a major component of woodsmoke. ELISA assays were used to assess levels of inflammatory cytokines (IL-8, IL-6, TNF-α), and cell viability was measured through LDH cytotoxicity assay. Cells were also cultured for 6 hours to assess inflammatory gene expression (COX-2, HO-1, IL-8, IL-6, and TNF-α) via RT-PCR, gel electrophoresis, and qPCR. Paeonol was found to be well tolerated by THP-1 cells, with minimal toxicity at the highest concentration (200 μM). Wood smoke was found to induce mRNA expression of IL-8, COX-2, and HO-1, indicating it induces inflammation via a NFĸB-mediated pathway. Additionally, paeonol was found to reduce inflammation induced by LPS, wood smoke, and acrolein in a dose-dependent manner, indicated by reduction in secreted IL-8 cytokine release as measured by ELISA. These data support paeonol as a potential treatment for lung inflammation induced by burning biomass fuels, and therefore chronic pulmonary disease associated with indoor air pollution. Further testing to confirm these findings is being conducted and to compare the anti-inflammatory effects of paeonol to other plant-derived anti-inflammatory compounds.

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