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Prostaglandin E2 Represses Interleukin 1 Beta-Induced Inflammatory Mediator Output From Pregnant Human Myometrial Cells Through the EP2 and EP4 Receptors.
MedLine Citation:
PMID:  22517618     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Inflammatory mediators including prostaglandins, cytokines and chemokines are strongly implicated in the mechanism of human labor, though their precise roles remain unknown. Here we demonstrate that interleukin 1 beta (IL-1beta) significantly increased the expression and release of interleukin-8 (CXCL8), monocyte chemotactic protein-1 (CCL2) and granulocyte macrophage colony stimulating factor (CSF2) by primary human myometrial cells. However, this effect was repressed by prostaglandin E(2) (PGE(2)). As PGE(2) can activate four distinct PGE(2) receptors (EP(1), EP(2), EP(3) and EP(4)) to elicit various responses, we sought to define the EP receptor(s) responsible for this repression. Using selective EP receptor agonists and a selective EP(4) antagonist, we show that PGE(2) mediates the repression of IL-1beta-induced release of CXCL8, CCL2 and CSF2 via activation of the EP(2) and EP(4) receptors. The use of siRNA gene-specific knockdown further confirmed a role for both receptors. Real-time RT-PCR demonstrated that EP(2) was the most highly expressed of all four EP receptors at the mRNA level in human myometrial cells and immunocytochemistry showed that EP(2) protein is abundantly present throughout the cells. Interestingly, PGE(2) does not appear to reduce mRNA expression of CXCL8, CCL2 and CSF2. Our results demonstrate that PGE2 can elicit anti-inflammatory responses via activation of the EP(2) and EP(4) receptors in lower segment term pregnant human myometrial cells. Further elucidation of the EP receptor-mediated signaling pathways in the pregnant human uterus may be beneficial for optimizing the maintenance of pregnancy, induction of labor, or indeed treatment of preterm labor.
Authors:
Andrea A Mosher; Kelly J Rainey; Mark A Giembycz; Stephen Wood; Donna M Slater
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-18
Journal Detail:
Title:  Biology of reproduction     Volume:  -     ISSN:  1529-7268     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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