title: Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by Pseudomonas aeruginosa via Inhibiting Overproduction of Prostaglandin E2.
abstract: BACKGROUND
  New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection.
  
  
  METHODS
  The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia.
  
  
  RESULTS
  ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2 ) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2 , ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well.
  
  
  CONCLUSIONS
  In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2 , which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa.
authors: Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.
authors: Yan-Xiong
authors: YX
authors: Mao
authors: Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors: Jin-Fu
authors: JF
authors: Xu
authors: Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, USA.
authors: Eric J
authors: EJ
authors: Seeley
authors: Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.
authors: Xiao-Dan
authors: XD
authors: Tang
authors: Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.
authors: Lu-Lu
authors: LL
authors: Xu
authors: Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.
authors: Ying-Gang
authors: YG
authors: Zhu
authors: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Yuan-Lin
authors: YL
authors: Song
authors: Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.|Department of Pulmonary Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Jie-Ming
authors: JM
authors: Qu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
chemical_list: D015232:Dinoprostone
keywords: Adipose tissue-derived mesenchymal stem cells; Prostaglandin E2; Pseudomonas aeruginosa; Pulmonary infection