Journal
CLINICAL IMMUNOLOGY
Volume 143, Issue 1, Pages 88-95Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2012.01.013
Keywords
TSLP; NME1; TIMP1; STAT3 pathway; Trophoblast invasion
Categories
Funding
- National Natural Science Foundation of China [31170870, 30200299, 30772033, 31101064]
- Education Ministry of China [200802461019, 20110071120092]
- Natural Science Foundation of Shanghai [10ZR1405100]
- Shanghai Health Bureau [2011Y081]
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Our previous study has demonstrated that TSLP induces the invasion of human trophoblasts and plays a role in embryo implantation. The present study is undertaken to explore the mechanism by which TSLP modulates trophoblast invasion. It was revealed that TSLP treatment significantly downregulated wNME1 and TIMP1 expression in both human trophoblasts and JEG-3 cells. The stimulatory effect of TSLP on trophoblast invasion was partially inhibited by either STAT3 inhibitor or STAT5 inhibitor. The downregulation of NME1 expression by TSLP was completely abrogated by STAT3 inhibitor. TIMP1 expression was attenuated by NME1 siRNA interference and enhanced by NME1 overexpression in JEG-3 cells. TSLP-stimulated increase in trophoblast invasion was partially attenuated by NME1 overexpression. Our data suggest that TSLP might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion. Our studies suggest that further studies on TSLP as a potential therapeutic for recurrent spontaneous abortion are warranted. (C) 2012 Elsevier Inc. All rights reserved.
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