Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways.
Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD). Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism. We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages. In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks. Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages. In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK. Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways. This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism.
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Wen
W
Gu
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Lin
L
Song
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Xiao-Ming
XM
Li
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Di
D
Wang
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Xue-Jun
XJ
Guo
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Wei-Guo
WG
Xu
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011656:Pulmonary Emphysema / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014184:Transplantation, Homologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone