Role of NF-[kappa]B pathway and potential of estrogen and its nanoformulation in sepsis
Loading...
Issue Date
2013
Authors
Almeshal, Nawaf '13
Degree
MS in Biotechnology
Advisor
Mousa, Shaker
Committee Members
Bharali, Dhrubar
Chaudry, Irshad
Thangirala, Sudha
Chaudry, Irshad
Thangirala, Sudha
Journal Title
Journal ISSN
Volume Title
Abstract
Sepsis is a common healthcare problem in the United States. Data have shown that women are affected with a lower incidence and fewer complications than men. This gender dimorphism has been attributed to estrogen. It has been shown that estrogen has many immunomodulatory functions, affecting many cytokines/chemokines. Our study focuses on whether the effects of estrogen in sepsis are genomic or non-genomic. HAEC cells were grown and treated with estradiol (works on nuclear and cytoplasmic receptors) and estradiol conjugated with nanoparticles (estradiol-NP, works exclusively on cytoplasmic receptors). Both formulations were tagged with Alexa Fluor\303\202\302\256488 dye, and confocal images of the cells were taken. Sepsis was induced in C57BL/6NHsd mice using the CLP model and in BALB/C-Tg (NF κB-RE-luc)-Xen mice using LPS. Effects of estradiol and estradiol-NP on IL-1, IL-6, IL-10, IL-17, TNF-α, and IFN-γ were evaluated by the multiplex cytokines assay. Effects on NF-κB were evaluated by IVIS Imaging and NF-κB Luciferase Reporter HeLa Stable Cell line. Confocal images confirmed that estradiol-NPs do not gain access to the nucleus. Estradiol and estradiol-NP significantly enhanced the production of IL-10, and estradiol-NP significantly enhanced production of IFN-γ. Estradiol suppresses NF-κB and enhances the production of IL-10 and IFN-γ likely via non-genomic pathways. Different doses given intravenously might be required to see effects on other cytokines and survival after CLP.
Citation
Almeshal, Nawaf. "Role of NF-[Kappa]B Pathway and Potential of Estrogen and Its Nanoformulation in Sepsis." Albany College of Pharmacy and Health Sciences, New York, Proquest/UMI, 2013.
ACPHS Research Commons URI
Description
Click on the Resource Link to find this item in the ACPHS Library catalog