Placental TLR/NLR expression signatures are altered with gestational age and inflammation. J Matern Fetal Neonatal Med 2017 Jul;30(13):1588-1595
Date
07/22/2016Pubmed ID
27440318DOI
10.1080/14767058.2016.1214705Scopus ID
2-s2.0-85016126125 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
OBJECTIVE: To quantify changes in placental expression of Toll-like receptors (TLRs) and nuclear oligomerization domain (NOD)-like receptors (NLRs) gene with (1) advancing gestational age (GA) and (2) exposure to chorioamnionitis (CA) and preterm premature rupture of membrane (PPROM).
METHODS: Placental tissue was collected at the time of birth from 83 subjects with live birth pregnancies from 24- to 40-week gestation between 2009 and 2013. Real-time RT-PCR analysis of 13 TLR/NLR genes involved in bacterial sensing was performed using specific probes.
RESULTS: Of 83 patients enrolled, 61 were preterm (<37 weeks). 23 (27%) had evidence of CA; and 33 (39.8%) had PPROM. 15 (18%) had both CA and PPROM (CP). 42 (50%) had neither CA nor PPROM (C/P). Only RIPK2 (p = 0.0025) and TLR4 (p = 0.0005) were found to increase progressively with GA. We found significant changes in TLR5 (p = 0.01) with CA, NFKBIA (p = 0.016) with PPROM, NKKBIA (p = 0.003), and NFKB1 (p = 0.009) with CA and PPROM.
CONCLUSION: RIPK2 (mediator of NOD-dependent NF-kB signaling) and TLR4 progressively increased with GA. We speculate this upregulation may be involved in initiating labor and delivery at term. Increase in NFKBIA seen in PPROM and CA might represent a counter regulatory mechanism to decrease inflammation in these conditions. This study provides new information on relationships between GA, CA/PPROM, and TLR/NLR signaling in the placenta.
Author List
Kumar N, Nandula P, Menden H, Jarzembowski J, Sampath VAuthor
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ChorioamnionitisFemale
Fetal Membranes, Premature Rupture
Gene Expression
Gestational Age
Humans
NF-kappa B
NLR Proteins
Placenta
Pregnancy
Real-Time Polymerase Chain Reaction
Receptor-Interacting Protein Serine-Threonine Kinase 2
Toll-Like Receptor 4
Toll-Like Receptors
Up-Regulation