Open AccessEffects of bone marrow‐derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF ‐ α , IL ‐1 β , and IFN ‐ γ
Author(s) -
Schwede Matthew,
Wilfong Erin M.,
Zemans Rachel L.,
Lee Patty J.,
Santos Claudia,
Fang Xiaohui,
Matthay Michael A.
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13831
Subject(s) - proinflammatory cytokine , stromal cell , mesenchymal stem cell , ards , tumor necrosis factor alpha , inflammation , downregulation and upregulation , immunology , biology , medicine , cancer research , microbiology and biotechnology , lung , gene , biochemistry
The acute respiratory distress syndrome ( ARDS ) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells ( MSC s) 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 MSC s 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 MSC s. 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 MSC s. 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 MSC s. In addition, MSC s 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.