Role of Peptidoglycan Recognition Proteins in Pathogenesis of Preeclampsia and Periodontitis.

Abstract

Preeclampsia (PE) is a pregnancy related disease and is the leading cause of maternal and fetal morbidity and mortality. Altered immune-inflammatory responses at the placental level in response to infectious agents (eg: periodontal pathogens) have been proposed to be etiological for this pregnancy complication. A new class of Pattern Recognition Receptors called Peptidoglycan Recognition Proteins (PGRP) constituting 4 distinct molecules PGRP 1-4 is emerging as key player in modulating host responses to peptidoglycan and its breakdown products. A critical knowledge gap exists on the role of PGRPs in the innate immune responses that occur at the maternal-fetal interface in response to pathogens and their components that may be present in maternal circulation secondary to chronic infections. The aim of this pilot study is to investigate the expression PGRPs in the placenta of pre-eclamptic women. This case control study consisted of subjects with: (1) normal term pregnancies (n=20) (2) pre-eclampsia (n=20). A real time quantitative PCR was used to analyze the relative mRNA expression of TLR2, TLR4, NOD1, NOD2, PGRP1, PGRP2, PGRP3, and PGRP4. Immunohistochemistry was performed to determine the cell type(s) expressing the PGRP proteins in the placental tissue. Summary statistics (mean, standard deviation, range, 95% confidence interval for the mean) were calculated for PGRP 1-4 expression for each group. The PCR data showed the expression of PGRPs 1, 3 and 4 when compared with positive controls such as liver, brain, skin and T-cells. This study demonstrated the expression of PGRPs 1, 3 and 4 by the placental samples. There was an up-regulation of PGRP-1 (1.4 fold) and down regulation of PGRP-3 (1.3 fold) and PGRP-4 (1.6 fold). TLR2, TLR4 and NOD2 mRNA were elevated in placental samples. The results from this novel research could lead to development of salivary and/or plasmatic biomarkers for early detection of PE and warrants further investigation. (This project is supported by the Delta Dental Master Thesis Award, No: 141031)