title: COX-2 plays a role in angiogenic DBA(+) uNK cell subsets activation and pregnancy protection in LPS-exposed mice.
abstract: 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).
  
  
  
  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.
  
  
  
  LPS caused sickness behavior, an immature DBA(+) uNK influx, decreased mature DBA(+) uNK cell numbers, and triggered a new DBA(low) 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.
  
  
  
  Collectively, our data indicate that COX-2 changes angiogenic DBA(+) uNK cells in order to protect mouse pregnancy after LPS injection.
authors.affiliation: Integrative Animal Biology Laboratory, Department for Cell and Developmental Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-000, Brazil. Electronic address: bruno_zavan@yahoo.com.br.
authors.forename: Bruno
authors.initials: B
authors.lastname: Zavan
authors.affiliation: Integrative Animal Biology Laboratory, Department for Cell and Developmental Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-000, Brazil. Electronic address: elianabiomed@gmail.com.
authors.forename: Eliana Martins
authors.initials: EM
authors.lastname: De Almeida
authors.affiliation: Integrative Animal Biology Laboratory, Department for Cell and Developmental Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-000, Brazil. Electronic address: evilasalles@gmail.com.
authors.forename: Évila da Silva Lopes
authors.initials: Éda S
authors.lastname: Salles
authors.affiliation: Integrative Animal Biology Laboratory, Department for Cell and Developmental Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-000, Brazil. Electronic address: amarantepaffaro@yahoo.com.br.
authors.forename: Andréa Mollica
authors.initials: AM
authors.lastname: do Amarante-Paffaro
authors.affiliation: Integrative Animal Biology Laboratory, Department for Cell and Developmental Biology, Biomedical Science Institute, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-000, Brazil. Electronic address: paffaroj@gmail.com.
authors.forename: Valdemar Antonio
authors.initials: VA
authors.lastname: Paffaro
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D005260:Female; D055809:Illness Behavior / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008098:Litter Size; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D054353:Perforin / Q000378:metabolism; D011247:Pregnancy; D013449:Sulfonamides / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000199:Actins; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013449:Sulfonamides; D054353:Perforin; D051546:Cyclooxygenase 2; C012655:nimesulide
keywords: Cyclooxygenase; Dolichos Biflorus agglutinin lectin; Inflammation; LPS; Nimesulide; Uterine natural killer