Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-7
pubmed:abstractText
There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial ?-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-?, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal-fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
980-6
pubmed:meshHeading
pubmed-meshheading:21677137-Animals, pubmed-meshheading:21677137-Animals, Newborn, pubmed-meshheading:21677137-Cell Line, pubmed-meshheading:21677137-Diaminopimelic Acid, pubmed-meshheading:21677137-Disease Models, Animal, pubmed-meshheading:21677137-Female, pubmed-meshheading:21677137-Humans, pubmed-meshheading:21677137-Infant, Newborn, pubmed-meshheading:21677137-Infant, Premature, pubmed-meshheading:21677137-Inflammation, pubmed-meshheading:21677137-Maternal-Fetal Exchange, pubmed-meshheading:21677137-Mice, pubmed-meshheading:21677137-Mice, Inbred C57BL, pubmed-meshheading:21677137-Nod1 Signaling Adaptor Protein, pubmed-meshheading:21677137-Obstetric Labor, Premature, pubmed-meshheading:21677137-Pregnancy, pubmed-meshheading:21677137-Pregnancy Outcome, pubmed-meshheading:21677137-Tissue Culture Techniques, pubmed-meshheading:21677137-Trophoblasts
pubmed:year
2011
pubmed:articleTitle
Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor.
pubmed:affiliation
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, New Haven, CT 06510, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't