Format

Send to

Choose Destination
Physiol Rep. 2018 Aug;6(16):e13831. doi: 10.14814/phy2.13831.

Effects of bone marrow-derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF-α, IL-1β, and IFN-γ.

Author information

1
Department of Medicine, University of California, San Francisco, California.
2
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
3
Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
4
Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, Michigan.
5
Section of Pulmonary, Critical Care & Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut.
6
Interdepartmental Division of Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
7
Division of Respirology, Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
8
Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
9
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California.
10
Department of Anesthesia, University of California, San Francisco, San Francisco, California.

Abstract

The acute respiratory distress syndrome (ARDS) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in animal models of ARDS, and their benefits occur in part through interactions with alveolar type II (ATII) cells. However, the effects that MSCs have on human ATII cells have not been well studied. Using previously published microarray data, we performed genome-wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to proinflammatory cytokines plus MSCs. Findings were validated by qPCR. Alveolar type II cells differentially expressed hundreds of genes when exposed either to proinflammatory cytokines or to proinflammatory cytokines plus MSCs. Stimulation with proinflammatory cytokines increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance. Some of these changes, including expression of some cytokines and genes related to surfactant, were reversed by exposure to MSCs. In addition, MSCs induced upregulation of other potentially beneficial genes, such as those related to extracellular matrix remodeling. We confirmed several of these gene expression changes by qPCR. Thus, ATII cells downregulate genes associated with surfactant and alveolar fluid clearance when exposed to inflammatory cytokines, and mesenchymal stromal cells partially reverse many of these gene expression changes.

KEYWORDS:

Acute respiratory distress syndrome; alveolar epithelial cells; cytokines; gene expression profiling; mesenchymal stromal cells

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center