Open AccessInflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate
Author(s) -
Michael Valentine,
Patrick Link,
Joseph Herbert,
Franck J. Kamga Gninzeko,
Matthew Schneck,
Keerthana Shankar,
Jewel Nkwocha,
Angela Reynolds,
Rebecca L. Heise
Publication year - 2018
Publication title -
cellular and molecular bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.668
H-Index - 34
eISSN - 1865-5033
pISSN - 1865-5025
DOI - 10.1007/s12195-018-0537-8
Subject(s) - proinflammatory cytokine , unfolded protein response , inflammation , endoplasmic reticulum , chemokine , monocyte , microbiology and biotechnology , homeostasis , ccl2 , lung , downregulation and upregulation , immunology , chemistry , medicine , biology , biochemistry , gene
Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation. ER stress is increased with aging and other pathological stimuli. We hypothesized that age and mechanical stretch increase alveolar epithelial cells' proinflammatory responses that are mediated by ER stress. Furthermore, we believed that inhibition of this upstream mechanism with 4PBA, an ER stress reducer, alleviates subsequent inflammation and monocyte recruitment.