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Sci Rep. 2018 Sep 10;8(1):13508. doi: 10.1038/s41598-018-32008-x.

Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells.

Author information

1
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America. marinamatsuda@northwestern.edu.
2
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
3
Department of Technology and Innovation, University of Southern Denmark, Odense, Denmark.
4
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, United States of America.
5
Department of Physical Sciences & Engineering, Wilbur Wright College, Chicago, Illinois, United States of America.
6
Division of Protein and Cellular Analysis, Thermo Fisher Scientific, Rockford, Illinois, United States of America.
7
Department of Chemistry, Northwestern University, Evanston, Illinois, United States of America.
8
Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, United States of America.
9
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
10
Jesse Brown VA Medical Center, Chicago, Illinois, United States of America.

Abstract

Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO2 for 24 h) vs normocapnia (5% CO2), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO2. These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.

PMID:
30202079
PMCID:
PMC6131151
DOI:
10.1038/s41598-018-32008-x
[Indexed for MEDLINE]
Free PMC Article

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