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. 2015:2015:316182.
doi: 10.1155/2015/316182. Epub 2015 May 14.

The Expression of Notch/Notch Ligand, IL-35, IL-17, and Th17/Treg in Preeclampsia

Weiping Cao  1 , Xinzhi Wang  2 , Tinmei Chen  1 , Huaying Zhu  1 , Wenlin Xu  3 , Songlan Zhao  4 , Xiaoqing Cheng  5 , Liangping Xia  5
Affiliations

The Expression of Notch/Notch Ligand, IL-35, IL-17, and Th17/Treg in Preeclampsia

Weiping Cao et al. Dis Markers. 2015.

Abstract

The aim of this study was to examine the interaction of Notch/Notch ligand with Th17/Treg, cytokines IL-35 and IL-17 in cases of preeclampsia (PE).

Methods: Peripheral blood was obtained from 42 PE patients and 22 health pregnant women. The mRNA expressions of Notch/Notch ligand, Treg transcription factor FoxP3 and Th17 transcription factor RORγt, EBI3 and P35 (IL-35 two subunits), and IL-17 were determined by qPCR. The serum levels of IL-17 and IL-35 were measured by ELISA.

Results: It was observed that the expressions of Foxp3, EBI3, and P35 in PE patients were lower compared with normal pregnancy, whereas the RORγt expression was significantly increased. The results also demonstrated that PE patients exhibited decreased levels of Treg-related cytokine IL-35, whereas IL-17 was significantly increased. PE patients expressed higher levels of Notch receptor (1-4) and Notch ligand of DLL4, whereas Notch ligand of Jagged-1, -2 was much lower. Furthermore, the levels of FoxP3 T cells correlated positively with Jagged-2. In addition, there were positive correlations between the mRNA level of IL-17 and DLL4.

Conclusion: Our results indicated that maternal immunological changes may reverse maternal tolerance in PE, and this phenomenon may due to the Th17/Treg imbalance affected by Notch/Notch ligand.

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Figures

Figure 1
Figure 1
Expression of transcription factors in PBMC of PE patients and normal pregnant women. mRNA expression in PBMC from PE patients was measured by PCR. The result was normalized relative to beta actin and compared to expression of these mRNA from 22 normal pregnant women. (a) The relative expression of Foxp3 was compared among three groups; (b) the relative expression of RORγt was compared among three groups.
Figure 2
Figure 2
mRNA expression of IL-17 and IL-35 in PBMC from preeclampsia and normal pregnant women. (a) The mRNA expression of IL-17. (b) IL-35 subunit P35. (c) The expression of EBI3mRNA was decreased in PBMC from preeclampsia compared with normal pregnant women.
Figure 3
Figure 3
Serum cytokine concentrations were determined from the peripheral blood samples obtained from preeclampsia patients and normal pregnancy. (a) The concentrations of serum interleukin-17 (IL-17) and (b) interleukin-35 (IL-35) were examined by enzyme-linked immunosorbent assay (ELISA) using specific cytokine detection kits.
Figure 4
Figure 4
mRNA expression of Notch receptor in PBMC from preeclampsia and normal pregnant women. (a) The mRNA expression of Notch1; (b) the mRNA expression of Notch2; (c) the mRNA expression of Notch3; (d) the mRNA expression of Notch4. The data were normalized to a housekeeping gene beta actin.
Figure 5
Figure 5
mRNA expression of Notch ligand in PBMC from preeclampsia and normal pregnant women. (a) The mRNA expression of Jagged-1; (b) the mRNA expression of Jagged-2; (c) the mRNA expression of DLL4. The data were normalized to a housekeeping gene beta actin.
Figure 6
Figure 6
As shown in (a), there were positive correlations between the mRNA of IL-17 and DLL4 (R = 0.3622, P < 0.05), as well as between Foxp3 and Jagged-2 of Notch ligands (R = 0.8384; P < 0.001) in the patients of severe PE (b). It appears that Notch signaling is involved in the regulation of peripheral induced Th17 and Treg cells in PE patients.
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