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Stem Cells. 2015 Jul;33(7):2331-42. doi: 10.1002/stem.1996. Epub 2015 May 13.

Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by Pseudomonas aeruginosa via Inhibiting Overproduction of Prostaglandin E2.

Author information

1
Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China.
2
Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
3
Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, USA.
4
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
5
Department of Pulmonary Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Abstract

RATIONALE:

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.

KEYWORDS:

Adipose tissue-derived mesenchymal stem cells; Prostaglandin E2; Pseudomonas aeruginosa; Pulmonary infection

PMID:
25788456
DOI:
10.1002/stem.1996
[Indexed for MEDLINE]
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