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

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.

• Authors: Yan-Xiong Mao, Jin-Fu Xu, Eric J Seeley, Xiao-Dan Tang, Lu-Lu Xu, Ying-Gang Zhu, Yuan-Lin Song, Jie-Ming Qu
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 33 Issue 7 Pg. 2331-42 (Jul 2015) ISSN: 1549-4918 [Electronic] England
• PMID: 25788456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 AlphaMed Press.

Chemical References

• Dinoprostone

Topics

• Adipose Tissue (metabolism)
• Animals
• Dinoprostone (metabolism)
• Disease Models, Animal
• Lung Diseases (genetics, metabolism, pathology)
• Male
• Mesenchymal Stem Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• Pseudomonas aeruginosa (pathogenicity)