Oncostatin M and TNF-α Induce Alpha-1 Antitrypsin Production in Undifferentiated Adipose Stromal Cells

Kevin Ni, Muhammad Umair Mukhtar Mian, Catherine Meador, Amar Gill, Daria Barwinska, Danting Cao, Matthew J. Justice, Di Jiang, Niccolette Schaefer, Kelly S. Schweitzer, Hong Wei Chu, Keith L. March, Irina Petrache

Research output: Contribution to journalArticle

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Abstract

Alpha-1 antitrypsin (A1AT), a circulating acute-phase reactant antiprotease, is produced and secreted by cells of endodermal epithelial origin, primarily hepatocytes, and by immune cells. Deficiency of A1AT is associated with increased risk of excessive lung inflammation and injury, especially following chronic cigarette smoke (CS) exposure. Exogenous administration of mesenchymal progenitor cells, including adipose tissue-derived stromal/stem cells (ASC), alleviates CS-induced lung injury through paracrine effectors such as growth factors. It is unknown, however, if mesodermal ASC can secrete functional A1AT and if CS exposure affects their A1AT production. Human ASC collected via liposuction from nonsmoking or smoking donors were stimulated by inflammatory cytokines tumor necrosis alpha (TNFα), oncostatin M (OSM), and/or dexamethasone (DEX) or were exposed to sublethal concentrations of ambient air control or CS extract (0.5%-2%). We detected minimal expression and secretion of A1AT by cultured ASC during unstimulated conditions, which significantly increased following stimulation with TNFα or OSM. Furthermore, TNFα and OSM synergistically enhanced A1AT expression and secretion, which were further increased by DEX. The A1AT transcript variant produced by stimulated ASC resembled that produced by bronchial epithelial cells rather than the variant produced by monocytes/macrophages. While the cigarette smoking status of the ASC donor had no measurable effect on the ability of ASC to induce A1AT expression, active exposure to CS extract markedly reduced A1AT expression and secretion by cultured ASC, as well as human tracheobronchial epithelial cells. ASC-secreted A1AT covalently complexed with neutrophil elastase in control ASC, but not in cells transfected with A1AT siRNA. Undifferentiated ASC may require priming to secrete functional A1AT, a potent antiprotease that may be relevant to stem cell therapeutic effects.

Original languageEnglish (US)
Pages (from-to)1468-1476
Number of pages9
JournalStem Cells and Development
Volume26
Issue number20
DOIs
StatePublished - Oct 15 2017

Fingerprint

Oncostatin M
alpha 1-Antitrypsin
Stromal Cells
Tumor Necrosis Factor-alpha
Smoke
Tobacco Products
Epithelial Cells
Lung Injury
Protease Inhibitors
Dexamethasone
Stem Cells
Smoking
alpha 1-Antitrypsin Deficiency
Lipectomy
Leukocyte Elastase
Aptitude
Acute-Phase Proteins
Therapeutic Uses
Mesenchymal Stromal Cells
Small Interfering RNA

Keywords

  • alpha-1-proteinase inhibitor
  • cigarette smoke
  • human adipose progenitor cell

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Oncostatin M and TNF-α Induce Alpha-1 Antitrypsin Production in Undifferentiated Adipose Stromal Cells. / Ni, Kevin; Umair Mukhtar Mian, Muhammad; Meador, Catherine; Gill, Amar; Barwinska, Daria; Cao, Danting; Justice, Matthew J.; Jiang, Di; Schaefer, Niccolette; Schweitzer, Kelly S.; Chu, Hong Wei; March, Keith L.; Petrache, Irina.

In: Stem Cells and Development, Vol. 26, No. 20, 15.10.2017, p. 1468-1476.

Research output: Contribution to journalArticle

Ni, K, Umair Mukhtar Mian, M, Meador, C, Gill, A, Barwinska, D, Cao, D, Justice, MJ, Jiang, D, Schaefer, N, Schweitzer, KS, Chu, HW, March, KL & Petrache, I 2017, 'Oncostatin M and TNF-α Induce Alpha-1 Antitrypsin Production in Undifferentiated Adipose Stromal Cells', Stem Cells and Development, vol. 26, no. 20, pp. 1468-1476. https://doi.org/10.1089/scd.2017.0099
Ni, Kevin ; Umair Mukhtar Mian, Muhammad ; Meador, Catherine ; Gill, Amar ; Barwinska, Daria ; Cao, Danting ; Justice, Matthew J. ; Jiang, Di ; Schaefer, Niccolette ; Schweitzer, Kelly S. ; Chu, Hong Wei ; March, Keith L. ; Petrache, Irina. / Oncostatin M and TNF-α Induce Alpha-1 Antitrypsin Production in Undifferentiated Adipose Stromal Cells. In: Stem Cells and Development. 2017 ; Vol. 26, No. 20. pp. 1468-1476.
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