Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 4, Pages 5106-5116Publisher
WILEY
DOI: 10.1002/jcp.27315
Keywords
interleukin; microRNA; preeclampsia; regulatory T-cell; T-helper 17 cell
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Funding
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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ProblemInappropriate activation of the immune system, particularly the imbalance of T-helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg-related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. MethodsExpressions of cytokines, specific transcription factors, and related miRNAs were measured by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test the interleukin (IL)-17, IL-23, IL-6, and IL-10 and transforming growth factor in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. ResultsPE patients exhibited a decreased number of Treg cells (p=0.006), while Th17 cells were increased (p=0.004). Forkhead box P3 and IL-10 mRNA expressions were reduced (p=0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor-related orphan nuclear receptor t, IL-17, IL-23, and IL-6 were enhanced (p<0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL-6, IL-17, and IL-23 (p=0.022, 0.0005, 0.0081, respectively), and decreased levels of IL-10 in the supernatant of PBMCs of PE patients compared with control group (p=0.0011). There was significant upregulation of miR-106b and miR-326 (p=0.0048 and 0.028, respectively) in PE patients in comparison with the control group. ConclusionsThese findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto-maternal immune cross-talk.
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