DOI
https://doi.org/10.25772/H25A-ZP40
Author ORCID Identifier
0000-0001-5049-7412
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Microbiology & Immunology
First Advisor
Patricia Sime
Abstract
Smoking is deleterious to our lungs and can precipitate in a multitude of diseases, including chronic obstructive pulmonary disease (COPD). COPD is primarily caused by smoking cigarettes and is a major public health issue. Current therapies only treat symptoms without halting or reversing disease progression, thus highlighting a large unmet need to develop new therapies. We address this gap by investigating maresin conjugate in tissue regeneration 3 (MCTR3) which is a newly discovered specialized pro-resoling mediator (SPM) that has the novel property of promoting tissue repair and regeneration in addition to being anti-inflammatory and pro-resolving. For the first time, we investigated MCTR3 in different models of cigarette smoke exposure in vitro and in vivo. MCTR3 dampened IL-8 responses in both M0 and M1 Thp-1 monocyte derived macrophages treated with cigarette smoke extract. MCTR3 also decreased IL-8 production in submerged small airway epithelial cells (SAECs) stimulated with IL-1β. We provide a detailed methodology on how to differentiate SAECs at the air-liquid interface, and demonstrate that MCTR3 dampened IL-8 production, protected against the loss of cilia and improved barrier function by decreasing apoptosis and increasing cell proliferation when given as a pre-treatment before cigarette smoke exposure. In the post-treatment regimen, MCTR3 also decreased IL-8 and restored the loss of cilia in differentiated SAECs. The acute 3-day cigarette smoke exposure model in vivo showed that MCTR3 decreased CXCL1 and showed trends in dampening leukocyte recruitment. In combination, these studies indicate that MCTR3 is capable of mitigating cigarette smoke-induced lung inflammation and damage.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-16-2025