IDSOG Abstract
Complement inhibitor CD55 and progesterone receptors as a novel therapeutic target for lipoxin A4 in endotoxin mediated inflammatory stress

https://doi.org/10.1016/j.ajog.2018.10.063Get rights and content

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Objectives

Endometrial inflammation and dysfunction is commonly implicated in multiple reproductive complications and leaves a lifelong mark on health. The CD55 glycoprotein protects the endometrium from complement’s lytic effect during inflammation. While Lipoxin A4 (LXA4) treatment had some anti-inflammatory success, the precise molecular target is not clear. The hypothesis for this study is that LXA4’s anti-inflammatory action is in part due to inhibition of complement activation, due to regulation of

Methods

Endometrial cell line, ECC1, a model system to study inflammation in relation to infertility and endometrial tissue disorder, was used in this study. ECC1 cells were treated with LXA4 alone and in the presence of a pro-inflammatory agent, lipopolysaccharide (LPS) in a time dependent manner. To evaluate CD55 and progesterone receptors (PR) levels, three independent methods were used: real-time PCR, Western blotting, and immunofluorescence. To investigate the molecular mechanism regulating the

Results

ECC1 cells treated with 1 uM LXA4 for 24 hours led to a significant increase in the levels of CD55 mRNA pool size and protein expression. Combined LPS plus LXA4 treatment also resulted in elevated sustained expression of CD55 at 24 and 48 hrs and increase of PR. ECC1 when pre-treated with LPS did not increase CD55 levels and lost PR. The pre-treatment of ECC1 cells with NFkB inhibitors attenuated LXA4 mediated CD55 increase, while LPS plus LXA4 did not.

Conclusions

Our results provide scientific evidence, that LXA4 support induction of complement inhibitor CD55 in the endometrium, even during pro-inflammatory LPS exposure. CD55 expression is critical for inhibition of complement’s lytic effects and prevention of neutrophils infiltration. LXA4 not only prevents the endometrium from losing PR during infection (exposure to LPS), but also stimulates PR expression after 48 hrs. Altogether this strongly suggests the therapeutic impact of LXA4 in the

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