Chemical chaperone TUDCA prevents apoptosis and improves survival during polymicrobial sepsis in mice
Journal Title
Scientific Reports
Publication Type
Journal Article
Abstract
Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice. Furthermore, in a 'two-hit' pneumonia model in mice, we have been able to demonstrate that administration of the chemical chaperone TUDCA helped to maintain lymphocyte homeostasis by significantly reducing lymphocyte apoptosis and this correlated with four-fold improvement in survival. Our results demonstrate a novel therapeutic opportunity for treating sepsis-induced lymphopenia in humans.
Publisher
Springer Nature
WEHI Research Division(s)
Infection And Immunity; Molecular Genetics Of Cancer
PubMed ID
27694827
Publisher's Version
https://doi.org/10.1038/srep34702
Open Access at Publisher's Site
http://www.nature.com/articles/srep34702
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-10-19 11:52:27
Last Modified: 2016-10-19 11:56:42
An error has occurred. This application may no longer respond until reloaded. Reload 🗙