Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.
Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.
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DOI：
10.1371/journal.pone.0123243
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Paria BC
中科院分区：
文献类型：
--
作者：
Lei W;Ni H;Herington J;Reese J;Paria BC
妊娠期间由于慢性或超生理水平的微生物感染而引起的过度细胞因子炎症反应会导致妊娠并发症，如早期妊娠缺陷/丢失和早产。细菌毒素脂多糖(LPS)长期以来被认为是一种强有力的促炎介质，已被确定为妊娠并发症的危险因素。碱性磷酸酶(AP)同工酶已被证明可通过去磷酸化来解毒。在这项研究中，我们研究了碱性磷酸酶(AP)在减轻脂多糖诱导的小鼠早期妊娠并发症中的作用。我们发现，1)着床前和着床后子宫分别产生内毒素识别和去磷酸化分子TLR4和组织非特异性AP(TNAP)同工酶；2)子宫TNAP同工酶使其产生部位的内毒素去磷酸化；3)当胚胎植入后给予内毒素在胚胎着床部位引起促炎细胞因子mRNA的表达并导致早孕丢失时，去磷酸化的内毒素既不会在胚胎着床部位触发促炎细胞因子mRNA的表达，也不会导致妊娠并发症；4)补充AP同工酶以加速内毒素的解毒可以减少胚胎植入后内毒素诱导的妊娠并发症。这些发现表明，使用AP同工酶的内毒素去磷酸化策略可能具有独特的治疗潜力，可以减轻高危女性由内毒素或革兰氏阴性细菌引起的妊娠并发症。
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.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
STAVINOHA, WB
DOI：
10.2147/ijwh.s24424
发表时间：
2011
期刊：
International journal of women's health
影响因子：
--
作者：
Hajishafiha M;Ghasemi-Rad M;Memari A;Naji S;Mladkova N;Saeedi V
通讯作者：
Saeedi V