Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.

Lei W, Ni H, Herington J, Reese J, Paria BC
PLoS One. 2015 10 (4): e0123243

PMID: 25910276 · PMCID: PMC4409290 · DOI:10.1371/journal.pone.0123243

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

MeSH Terms (21)

Alkaline Phosphatase Animals Disease Models, Animal Embryo Implantation Enzyme Activation Female Gene Expression Inflammation In Situ Hybridization Isoenzymes Lipopolysaccharide Receptors Lipopolysaccharides Mice Myeloid Differentiation Factor 88 Phosphorylation Pregnancy Pregnancy Complications Real-Time Polymerase Chain Reaction RNA, Messenger Toll-Like Receptor 4 Uterus

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