title: Adrenaline stimulates the proliferation and migration of mesenchymal stem cells towards the LPS-induced lung injury.
abstract: 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 μM enhanced proliferation of BMSCs through both α- and β-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.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
authors.forename: Mengjia
authors.initials: M
authors.lastname: Qian
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D004837:Epinephrine
keywords: acute lung injury; adrenergic receptor agonists; inflammation; lipopolysaccharide; mesenchymal stem cells