Description
- Abstract:
- Sepsis is defined as a state of life-threatening organ dysfunction due to dysregulated host response to infection. Because of its complex pathogenesis, sepsis is difficult to both diagnose and treat. In order to develop a viable therapeutic for sepsis, we must work to understanding its underlying mechanisms. Programmed Cell Death Receptor 1 (PD-1) and its ligands, PD-L1 and PD-L2, have been studied in sepsis for their therapeutic effects. We have seen in our results that PD-L2 appears to be down-regulated in sepsis, and its expression was shown to change primarily in the liver. The liver is an organ whose dysfunction is strongly associated with mortality, as it plays a key role in metabolic and homeostatic activities. Understanding the pathophysiology of liver failure during sepsis will serve to develop a more efficient method of diagnosing liver dysfunction and encourage patient survival. Therefore, our central hypothesis is that sepsis-induced change in PD-L2 expression in the liver should contribute to altered liver function and subsequently, altered general morbidity/mortality. In our study, we compared PD-L2-/-, PD-L1-/- and wild type mice to assess differences in survival, liver function, and overall impacts on septic outcomes. What we found was in support of our hypothesis; PD-L2 appeared to worsen liver function. Interestingly, we also saw some protective effects of PD-L2 knockout, namely in the case of bacterial clearance. PD-L2’s exact roles and underlying mechanisms of action are still unclear, but our study provided a strong foundation for us to answer these questions in the future.
- Notes:
- Thesis (Sc. M.)--Brown University, 2017
Access Conditions
- Rights
- In Copyright
- Restrictions on Use
- Collection is open for research.
Citation
Le, Marilyn C.,
"A Novel Role for Programmed Cell Death Receptor Ligand 2 (PD-L2) in Sepsis-Induced Hepatic Dysfunction"
(2017).
Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z05B00WQ
Relations
Collection:
-
Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations
Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department....