Keywords
Inflammation; RIP2; 5LO; NOD2; RIPK2
Abstract
Although inflammation plays a key role in our body’s defenses, chronic inflammation can lead to the progression of various diseases, such as irritable bowel disease, arthritis and asthma. Due to this, extensive effort has been put into understanding not only how inflammation is initiated but also how it is resolved. One pathway with established ties to inflammation is the Nucleotide-binding Oligomerization Domain-Containing Protein 2 (NOD2) pathway. Binding of peptidoglycan by the NOD2 receptor promotes the recruitment of Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIP2 or RIPK2). RIP2 transduces downstream signals leading to Nuclear Factor Kappa B (NF-kB) activation and the production of antimicrobial peptides and proinflammatory cytokines to mediate immune defense. Due to the involvement of NOD2 in inflammatory disease, there has been great interest in targeting this pathway through pharmacological inhibition of RIP2. Prior studies in our laboratory have demonstrated that RIP2 can also promote phosphorylation and enzymatic activation of Arachidonate 5-Lipoxygenase (5LO or ALOX5), an enzyme important for the production of both pro-inflammatory and pro-resolution lipid mediators. The efficacy of various RIP2-targeted therapies are based on their ability to reduce NF-kB activation and pro-inflammatory cytokine secretion. However, nothing yet is known about how such inhibitors affect 5LO activity. To investigate this question, we utilized transient transfection, SDS/PAGE, Western Blotting and protein interaction assays to assess the effects of RIP2 inhibitors on the activation of 5LO. Our data so far indicates that RIP2 inhibitors with different mechanisms of action do exhibit differential effects on 5LO phosphorylation. These findings will have potential implications for testing, development and use of such inhibitors for treatment of inflammatory diseases.
Thesis Completion Year
2024
Thesis Completion Semester
Spring
Thesis Chair
Tigno-Aranjuez, Justine
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Biomedical Sciences
Language
English
Access Status
Campus Access
Length of Campus Access
3 years
Campus Location
Orlando (Main) Campus
STARS Citation
Burleson, Hannah, "The Effect of Pharmacological Inhibition of Receptor-Interacting Serine/Threonine Protein Kinase 2 on the Enzymatic Activity of Arachidonate 5-Lipoxygenase" (2024). Honors Undergraduate Theses. 23.
https://stars.library.ucf.edu/hut2024/23