title: The negative regulators of the host immune response: an unexplored pathway in preterm birth.
abstract: OBJECTIVE
  Toll-like receptors (TLRs) are essential mediators of host immunity. TLR activation must be tightly regulated to prevent an exaggerated immune response from devastating the host. These studies assessed the expression of negative regulators (interleukin receptor-associated kinase [IRAK]-3, IRAK-1, Fas-associated protein with death domain) during pregnancy and in preterm birth (PTB).
  
  
  METHODS
  Tissues (uterine, cervix, placenta, and spleens) from the following experimental groups were harvested: (1) nonpregnant mice, (2) pregnant mice across gestation, (3) murine model of PTB, and (4) pregnant mice exposed to medroxyprogesterone acetate (MPA).
  
  
  RESULTS
  Negative regulators are differentially expressed in the uterus during pregnancy. In the setting of PTB, IRAK-3 is significantly increased in the uterus and cervix but not the placenta. In maternal spleens, IRAK-3 and IRAK-1 are increased in response to intrauterine inflammation. MPA can increase IRAK expression in cervical tissues.
  
  
  CONCLUSIONS
  Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Lyttle
authors.forename: Jinghua
authors.initials: J
authors.lastname: Chai
authors.forename: Juan M
authors.initials: JM
authors.lastname: Gonzalez
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Mary
authors.initials: M
authors.lastname: Sammel
authors.forename: Michal A
authors.initials: MA
authors.lastname: Elovitz
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism; D004195:Disease Models, Animal; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D053200:Fas-Associated Death Domain Protein; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; C507772:Irak3 protein, mouse