학술논문

Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Document Type
research-article
Author
Zhihong Yuan, author; Brahmchetna Bedi, author; Ruxana T. Sadikot, author
Source
Journal of Visualized Experiments. (135)
Subject
Genetics
Issue 135
Exosomes
microRNAs
miR-155
miR-146a
LPS
lung
sepsis
Language
English
ISSN
1940-087X
Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogeneous group of lung diseases which continues to have a high morbidity and mortality. The molecular pathogenesis of ALI is being better defined; however, because of the complex nature of the disease molecular therapies have yet to be developed. Here we use a lipopolysaccharide (LPS) induced mouse model of acute septic lung injury to delineate the role of exosomes in the inflammatory response. Using this model, we were able to show that mice that are exposed to intraperitoneal LPS secrete exosomes in Broncho-alveolar lavage (BAL) fluid from the lungs that are packaged with miRNA and cytokines which regulate inflammatory response. Further using a co-culture model system, we show that exosomes released from macrophages disrupt expression of tight junction proteins in bronchial epithelial cells. These results suggest that 1) cross talk between innate immune and structural cells through the exosomal shuttling contribute to the inflammatory response and disruption of the structural barrier and 2) targeting these miRNAs may provide a novel platform to treat ALI and ARDS.