Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs

Andrea M. Foskett, Nikolay Bazhanov, Xinyu Ti, April Tiblow, Thomas J. Bartosh, Darwin J. Prockop

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-α-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bleomycin-induced lung injury with systemic TSG-6 administration may produce therapeutic effects such as preventing the deterioration of lung function and increasing survival by modulation of the inflammatory cascade. Lung injury in C57Bl/6J mice was induced by intratracheal administration of bleomycin. Mice then received intravenous injections of TSG-6 or sham controls. Pulse oximetry was used to monitor changes in lung function. Cell infiltration was evaluated by flow cytometry, cytokine expression was measured by ELISA assays, and lungs were assessed for histological attributes. The results demonstrated that intravenous infusion of TSG-6 during the early inflammatory phase decreased cellular infiltration into alveolar spaces. Most importantly, it improved both the subsequent decrease in arterial oxygen saturation levels and the survival of the mice. These findings demonstrated that the beneficial effects of TSG-6 in a model of bleomycin-induced lung injury are largely explained by the protein modulating the early inflammatory phase. Similar phase-directed strategy with TSG-6 or other therapeutic factors that MSCs produce may be useful for other lung diseases and diseases of other organs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume306
Issue number2
DOIs
StatePublished - Jan 15 2014
Externally publishedYes

Fingerprint

Bleomycin
Inflammation
Lung
Lung Injury
Multipotent Stem Cells
Adult Stem Cells
Proteins
Stem Cells
Therapeutics
Oximetry
Therapeutic Uses
Intravenous Infusions
Intravenous Injections
Lung Diseases
Flow Cytometry
Bone Marrow
Enzyme-Linked Immunosorbent Assay
Cytokines
Oxygen

Keywords

  • Inflammation
  • Lung injury
  • Mesenchymal stromal cells
  • Pulmonary gas exchange

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Phase-directed therapy : TSG-6 targeted to early inflammation improves bleomycin-injured lungs. / Foskett, Andrea M.; Bazhanov, Nikolay; Ti, Xinyu; Tiblow, April; Bartosh, Thomas J.; Prockop, Darwin J.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 306, No. 2, 15.01.2014.

Research output: Contribution to journalArticle

Foskett, Andrea M. ; Bazhanov, Nikolay ; Ti, Xinyu ; Tiblow, April ; Bartosh, Thomas J. ; Prockop, Darwin J. / Phase-directed therapy : TSG-6 targeted to early inflammation improves bleomycin-injured lungs. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2014 ; Vol. 306, No. 2.
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