Journal article
Inflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate
Cellular and molecular bioengineering, Vol.11(6), pp.495-508
12/01/2018
DOI: 10.1007/s12195-018-0537-8
PMCID: PMC6301058
PMID: 30581495
Abstract
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.
Type II alveolar epithelial cells (ATII) were harvested from C57Bl6/J mice 2 months (young) and 20 months (old) of age. The cells were cyclically stretched at 15% change in surface area for up to 24 h. Prior to stretch, groups were administered 4PBA or vehicle as a control.
Mechanical stretch and age upregulated ER stress and proinflammatory MCP-1/CCL2 and MIP-1 beta/CCL4 chemokine expression in ATIIs. Age-matched and mismatched monocyte recruitment by ATII conditioned media was also quantified.
Age increases susceptibility to stretch-induced ER stress and downstream inflammatory gene expression in a primary ATII epithelial cell model. Administration of 4PBA attenuated the increased ER stress and proinflammatory responses from stretch and/or age and significantly reduced monocyte migration to ATII conditioned media.
Details
- Title: Subtitle
- Inflammation and Monocyte Recruitment Due to Aging and Mechanical Stretch in Alveolar Epithelium are Inhibited by the Molecular Chaperone 4-Phenylbutyrate
- Creators
- M. S. Valentine - Virginia Commonwealth UniversityP. A. Link - Virginia Commonwealth UniversityJ. A. Herbert - Virginia Commonwealth UniversityF J Kamga Gninzeko - Virginia Commonwealth UniversityM. B. Schneck - Virginia Commonwealth UniversityK. Shankar - Virginia Commonwealth UniversityJ. Nkwocha - Virginia Commonwealth UniversityA. M. Reynolds - Virginia Commonwealth UniversityR. L. Heise - Virginia Commonwealth University
- Resource Type
- Journal article
- Publication Details
- Cellular and molecular bioengineering, Vol.11(6), pp.495-508
- DOI
- 10.1007/s12195-018-0537-8
- PMID
- 30581495
- PMCID
- PMC6301058
- NLM abbreviation
- Cell Mol Bioeng
- ISSN
- 1865-5025
- eISSN
- 1865-5033
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- CMMI-1351162 / National Science Foundation; National Science Foundation (NSF) R01AG041823 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984948041302771
Metrics
3 Record Views