Expression of nuclear factor of activated T cells 5 and monocyte chemoattractant protein-1 and their relationship with macrophage infiltration in placenta of severe preeclampsia

Abstract

Objective To explore the relationship between expression of nuclear factor of activated T cells 5 (NFAT5), monocyte chemoattractant protein-1(MCP-1) and CD68 marked macrophages in placental tissues of severe preeclampsia (sPE) . Methods Placental samples were collected from 30 normal ful-term healthy singleton pregnant women (control group), 31 singleton pregnant women with early-onset sPE(EPE) and 30 patients with late-onset sPE(LPE) who underwent elective cesarean section in the Third Affiliated Hospital of Zhengzhou University between January 2015 and January 2016. Immunohistochemistry was used to detect the expression and distribution of NFAT5 and MCP-1 in placental tissues and CD68 marked macrophage in decidual tissues. Real time-polymerase chain reaction technique was applied to analyze the expression of NFAT5 mRNA and MCP-1 mRNA in placental tissues. The correlations between placental NFAT5 mRNA and MCP-1 mRNA levels and CD68 marked macrophage were analyzed. One-way ANOVA, t-test, Chi-square test and Pearson's correlation analysis were used for statistics. Results (1) In all of the three groups, NFAT5 protein was expressed in nucleus and cytoplasm of syncytiotrophoblast cells, but less expressed in villi vascular endothelial cells; MCP-1 protein was expressed in cytoplasm of both syncytiotrophoblast cells and villi vascular endothelial cells. Positive NFAT5 expression rate in the EPE group was higher than in the LPE group [94%(29/31) vs 70%(21/30), χ2=5.720, P=0.017] and the control group [53%(16/30), χ2=12.743, P=0.001], respectively, the same results were abtained for MCP-1 expression [90%(28/31) vs 70%(21/30) and 43%(13/30), χ2=3.985 and 15.276, P=0.046 and 0.001]. (2) The NFAT5 mRNA level was higher in the EPE group than in the LPE and control group (1.07±0.03 vs 0.92±0.02 and 0.90±0.04, both P=0.001), respectively, and so was the MCP-1 mRNA level (1.08±0.12 vs 1.02±0.08 and 0.99±0.02, both P=0.001), respectively. (3) The number of macrophage in the EPE group was higher than that in the LPE group [(26.18±1.17) vs (9.78±0.31), t=75.358, P<0.001], and that in the LPE group was higher than that in the control group (9.78 ±0.31 vs 9.47±0.61, t=2.481, P<0.05). (4) In the EPE group, the expression of NFAT5 mRNA was positively correlated with the expression of both MCP-1 mRNA (r=0.554, P=0.001) and macrophage count (r=0.527, P=0.003). However, the level of MCP-1 mRNA was positively correlated with macrophage count only (r=0.395, P=0.031). Conclusions The increased expression of NFAT5 and MCP-1 in the placenta of patients with sPE, especially in the EPE, implies that NFAT5 and MCP-1 may contribute to the pathogenesis of EPE. Key words: Pre-eclampsia; NFATC transcription factors; Chemokine CCL2; Macrophages