title: NOD1 expression elicited by iE-DAP in first trimester human trophoblast cells and its potential role in infection-associated inflammation.
abstract: OBJECTIVE
  The underlying mechanisms of protective immunity of placental trophoblast cells against bacterial infection remain largely unknown. NOD1 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. This study aimed to investigate the expression and function of NOD1 in first trimester trophoblast cells, and evaluate the potential role of trophoblast cells in infection-associated inflammation.
  
  
  METHODS
  Human extravillous trophoblast cell line HTR8 cells were stimulated with various concentrations of iE-DAP for various periods of time. NOD1 expression was detected by immunofluorescence, and the changes in NOD1 and RICK mRNA and protein in H8 cells were determined by real-time polymerase chain reaction and Western blot analysis. The concentrations of interleukin (IL)-8 and IL-6 secreted by H8 cells were examined by enzyme-linked immunosorbent assay. NF-κB transcription activity and P65 expression were detected by electrophoretic mobility shift assay and Western blot analysis.
  
  
  RESULTS
  H8 cells expressed NOD1, and the effects of iE-DAP on NOD1 were dose- and time-dependent. The concentration of IL-8 increased gradually with increasing concentration of iE-DAP, and the levels of IL-8 and IL-6 were associated with the duration of exposure to iE-DAP. The dose of iE-DAP was significantly associated with expression of RICK and P65, and stimulation of H8 cells by iE-DAP altered NF-κB transcription activity.
  
  
  CONCLUSIONS
  NOD1 may have a role in mediating infection-associated inflammation. Once iE-DAP is recognized by NOD1, the inflammatory response may be induced via NOD1-RICK-NF-κB-mediated pathways.
authors.affiliation: Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Guan
authors.forename: A
authors.initials: A
authors.lastname: Xing
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Xiong
authors.forename: B
authors.initials: B
authors.lastname: Peng
mesh_terms: D002460:Cell Line; D002821:Chorioamnionitis / Q000378:metabolism*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D003960:Diaminopimelic Acid; C034331:N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2
keywords: Cytokines; HTR8; NF-κB; Nuclear oligomerization domain 1; RICK; iE-DAP