Health, Exercise, and Sports Sciences ETDs
Publication Date
Spring 5-13-2025
Abstract
Toll-like receptor 4 (TLR4) activation increases pro-inflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Exercise is recommended to reduce TLR4 expression and intracellular signaling, but the mechanisms for how this occurs are unknown, and even less is known regarding the effect of exercise on TLR4 expressed in skeletal muscle. Activation of TLR4 expressed on skeletal muscle can elicit local metabolic and atrophic effects in addition to systemic inflammation from TLR4 activation on immune cells. Therefore, the purpose of this dissertation project is to better uncover the nature and mechanisms by which exercise affects TLR4 expression and intracellular signaling in different cell types (peripheral blood mononuclear cells: PBMCs and skeletal muscle) using cell culture and human experiments. In this project, we showed that in an in vitro model of muscle contraction, repeated myotube contractions can prevent TLR4-mediated myotube atrophy, partially due to decreasing membrane-bound TLR4 and increasing soluble TLR4 (sTLR4). Next, we provided evidence that divergent mechanisms may regulate TLR4 expression on PBMCs by augmenting membrane-bound and soluble TLR4 expressions following workload-matched exercise in normoxic and hypoxic environments. Finally, we demonstrated that TLR4 receptor regulation and cellular signaling responses to vigorous exercise are dependent on training status (endurance-trained vs untrained) but not tissue type (PBMCs vs skeletal muscle). Together these studies provide a better understanding of TLR4 regulation in response to an acute bout of exercise in different tissue types and how endurance training may affect these responses.
Keywords
atrophy, inflammation, skeletal muscle, PBMCs, LPS
Document Type
Dissertation
Language
English
Degree Name
Physical Education, Sports and Exercise Science
Level of Degree
Doctoral
Department Name
Health, Exercise, and Sports Sciences
First Committee Member (Chair)
Michael Deyhle
Second Committee Member
Christine Mermier
Third Committee Member
Fabiano Amorim
Fourth Committee Member
Roberto Nava
Fifth Committee Member
Orlando Laitano
Recommended Citation
Ducharme, Jeremy B.. "Exercise and Its Regulation of Toll-Like Receptor 4 Expression and Intracellular Signaling." (2025). https://digitalrepository.unm.edu/educ_hess_etds/164
