Mesenchymal stem cells reduce cigarette smoke-induced inflammation and airflow obstruction in rats via TGF-β1 signaling.
Cigarette smoke has been shown to cause chronic inflammation of the lungs, eventually leading to chronic obstructive pulmonary disease (COPD). Additionally, recent studies have suggested that mesenchymal stem cells (MSCs) can mediate local inflammatory responses in the lungs. Thus, the aim of the present study was to test the effects of rat MSCs (rMSCs) on inflammation of the lungs and destructive pulmonary function induced by cigarette smoke in rats. Rats were exposed to cigarette smoke for 7 weeks. rMSCs were cultured in vitro and infused intratracheally into cigarette smoke-exposed rats. The total and differential cell counts in the bronchoalveolar lavage fluid (BALF), histological changes, pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) expression, and pulmonary function were evaluated. Additionally, human peripheral blood mononuclear cells and human MSCs were cocultured in vitro to detect cytokines and TGF-β1 levels. We found that rMSC administration resulted in downregulation of pro-inflammatory cytokines in the lungs while increasing TGF-β1 expression, reducing total inflammatory cell numbers in the BALF, and improving pulmonary histopathology and airflow obstruction. Coculture revealed that human MSCs mediated an anti-inflammatory effect partly via upregulation of TGF-β1. These findings suggested that MSCs may have therapeutic potential in cigarette smoke-induced inflammation and airflow obstruction, partly via upregulation of TGF-β1.
Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai 200092 , China.
Lin
L
Song
Xiao-jun
XJ
Guan
Xi
X
Chen
Zhi-lei
ZL
Cui
Feng-feng
FF
Han
Xue-jun
XJ
Guo
Wei-guo
WG
Xu
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000276:immunology; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D014132:Trachea; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; D012906:Smoke; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
inflammation; mesenchymal stem cell; transforming growth factor-β1