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- Title
Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by P seudomonas aeruginosa via Inhibiting Overproduction of Prostaglandin E<sub>2</sub>.
- Authors
Mao, Yan-Xiong; Tang, Xiao-Dan; Xu, Lu-Lu; Zhu, Ying-Gang; Qu, Jie-Ming; Xu, Jin-Fu; Seeley, Eric J.; Song, Yuan-Lin
- Abstract
A bstract 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. S tem C ells 2015;33:2331-2342
- Subjects
ADIPOSE tissues; STEM cells; LUNG infections
- Publication
Stem Cells, 2015, Vol 33, Issue 7, p2331
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1996