Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 18, Issue 8, Pages 1612-1622Publisher
WILEY
DOI: 10.1111/jcmm.12283
Keywords
acute lung injury; mesenchymal stem cells; lipopolysaccharide; inflammation; adrenergic receptor agonists
Categories
Funding
- Shanghai Leading Academic Discipline Project [B115]
- Shanghai Young Clinicians Nurturing Plan
- National Nature Science Foundation of China [91230204, 81270099, 81320108001]
- Shanghai Committee of Science and Technology [12JC1402200, 12431900207, 11410708600]
- Zhongshan Distinguished Professor Grant
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Bone marrow-derived mesenchymal stem cells (BMSCs) could modulate inflammation in experimental lung injury. On the other hand, adrenergic receptor agonists could increase DNA synthesis of stem cells. Therefore, we investigated the therapeutic role of adrenaline-stimulated BMSCs on lipopolysaccharide (LPS)-induced lung injury. BMSCs were cultured with adrenergic receptor agonists or antagonists. Suspensions of lung cells or sliced lung tissue from animals with or without LPS-induced injury were co-cultured with BMSCs. LPS-stimulated alveolar macrophages were co-cultured with BMSCs (with adrenaline stimulation or not) in Transwell for 6 hrs. A preliminary animal experiment was conducted to validate the findings in ex vivo study. We found that adrenaline at 10 mu M enhanced proliferation of BMSCs through both alpha- and beta-adrenergic receptors. Adrenaline promoted the migration of BMSCs towards LPS-injured lung cells or lung tissue. Adrenaline-stimulated BMSCs decreased the inflammation of LPS-stimulated macrophages, probably through the expression and secretion of several paracrine factors. Adrenaline reduced the extent of injury in LPS-injured rats. Our data indicate that adrenaline-stimulated BMSCs might contribute to the prevention from acute lung injury through the activation of adrenergic receptors, promotion of proliferation and migration towards injured lung, and modulation of inflammation.
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