COX-2 plays a role in angiogenic DBA+ uNK cell subsets activation and pregnancy protection in LPS-exposed mice

Bruno Zavan, Eliana Martins De Almeida, Évila Da Silva Lopes Salles, Andréa Mollica Do Amarante-Paffaro, Valdemar Antonio Paffaro

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Introduction Although uterine Natural Killer (uNK) cells have cytoplasmic granules rich in perforin and granzymes, these cells do not degranulate in normal pregnancy. DBA lectin+ uNK cells produce angiogenic factors which stimulate remodeling of uterine arterioles to increase blood flow within the growing feto-placental unit. We sought to investigate the importance of COX-2 on mouse pregnancy inoculated with Gram-negative bacteria Lipopolysaccharide (LPS) by treating with a selective COX-2 inhibitor (nimesulide). Methods We have combined histochemical, immunohistochemical, stereological, morphometric, behavioral, and litter analyses to investigate mouse pregnancy inoculated with LPS with or without pre-treatment with nimesulide 30 min before LPS injections, focusing on DBA+ uNK cell response and viability of the pregnancy. Results LPS caused sickness behavior, an immature DBA+ uNK influx, decreased mature DBA+ uNK cell numbers, and triggered a new DBAlow uNK appearance. These effects of LPS, except the sickness behavior, were prevented by nimesulide. COX-2 inhibition also prevented the down-regulation of uNK perforin and spiral arteriole α-actin expression stimulated by LPS. While the litter size from Nimesulide + LPS-treated mothers was significantly smaller compared to those from LPS-treated group, nimesulide alone showed no effect on the offspring. Discussion Collectively, our data indicate that COX-2 changes angiogenic DBA+ uNK cells in order to protect mouse pregnancy after LPS injection.

Original languageEnglish (US)
Pages (from-to)34-45
Number of pages12
StatePublished - Aug 1 2016
Externally publishedYes


  • Cyclooxygenase
  • Dolichos Biflorus agglutinin lectin
  • Inflammation
  • LPS
  • Nimesulide
  • Uterine natural killer

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology


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