Related Experiment Video
Updated: May 10, 2026

Isolation of Leukocytes from the Human Maternal-fetal Interface
Published on: May 21, 2015
NOD1 and NOD2 regulate proinflammatory and prolabor mediators in human fetal membranes and myometrium via nuclear
1Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, 163 Studley Rd., Melbourne, VIC 3084, Australia. mlappas@unimelb.edu.au
Abstract:
Preterm birth remains one of the most important issues facing perinatal medicine today, with chronic inflammation and/or infection being the biggest etiological factor. The nucleotide oligomerization domain (NOD) intracellular molecules recognize a wide range of microbial products as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor KB (NFKB), a central regulator of the terminal processes of human labor and delivery. The aims of this study were to determine the effect of 1) human labor, proinflammatory cytokines, and bacterial endotoxin LPS on NOD1 and NOD2 expression and 2) NOD1 and NOD2 activation on the expression of prolabor mediators in human fetal membranes and myometrium. NOD1 and NOD2 expression was significantly higher in fetal membranes and myometrium after spontaneous labor when compared to nonlaboring tissues. Bacterial endotoxin LPS and the proinflammatory cytokines TNF and IL1B significantly increased NOD2, but not NOD1, expression. Furthermore, LPS-induced NOD2 expression was decreased by the NFKB inhibitor BAY 11-7082. In both fetal membranes and myometrium, the NOD1 ligand bacterial iE-DAP and the NOD2 ligand bacterial MDP significantly increased the expression and secretion of proinflammatory cytokines (IL6 and IL8), cyclooxygenase (PTGS2) expression and subsequent release of prostaglandins PGE2 and PGF2alpha, and the expression and activity of MMP9. The effects of these NOD1 and NOD2 ligands were mediated via NFKB, as 1) both iE-DAP and MDP significantly increased NFKB activation and 2) the NFKB inhibitor BAY 11-7082 attenuated iE-DAP- and MDP-induced expression and secretion of prolabor mediators. In conclusion, NOD1 and NOD2 are increased in laboring fetal membranes and myometrium and with bacterial infection. Agonist activation of NOD1 and NOD2 by bacterial products leads to NFKB activation and transcription of NFKB induced prolabor genes. NOD1 and NOD2 may thus represent therapeutic targets for the treatment and/or management of preterm birth.
More Related Videos
07:37Isolation of Primary Human Decidual Cells from the Fetal Membranes of Term Placentae
Published on: April 30, 2018
09:12Assessing Cellular Stress and Inflammation in Discrete Oxytocin-secreting Brain Nuclei in the Neonatal Rat Before and After First Colostrum Feeding
Published on: November 14, 2018
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of Nuclear Protein Sorting
NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Nitric Oxide Signaling Pathway
Regulation of Angiogenesis and Blood Supply
TGF - β Signaling Pathway