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Placental TLR/NLR expression signatures are altered with gestational age and inflammation. J Matern Fetal Neonatal Med 2017 Jul;30(13):1588-1595

Date

07/22/2016

Pubmed ID

27440318

DOI

10.1080/14767058.2016.1214705

Scopus ID

2-s2.0-85016126125 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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 V

Author

Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Chorioamnionitis
Female
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