Zhengping Wang

Placental imbalance of Th1- and Th2-type cytokines in preeclampsia

Objectives.  To characterize the changes in the level of T helper 1 (Th1)‐ [interleukin (IL)‐2 and tumor necrosis factor (TNF)‐α] and Th2‐type cytokine (IL‐10) and the ratios of Th1/Th2 (IL‐2/IL‐10 and TNF‐α/IL‐10) in placentae from women with preeclampsia and women with gestational hypertension.

Serum visfatin levels in late pregnancy and pre-eclampsia.

Objectives. To characterise the changes in serum visfatin levels in late normal pregnancy and pre‐eclampsia. Methods. Twenty‐seven women with pre‐eclampsia were recruited. Twenty‐eight women in the third trimester of normal pregnancy served as pregnant control and 28 healthy non‐pregnant women as non‐pregnant control. Serum levels of visfatin were measured with an enzyme‐linked immunosorbent assay. Results. The means of serum visfatin were 626.4±45.5ng/ml (mean±SEM) in non‐pregnant control, 695.9±92.5ng/ml in pregnant control, and 308.3±80.0 ng/ml in pre‐eclampsia, respectively, and were significantly different among the groups (p <0.001). Visfatin level was significantly lower in pre‐eclampsia compared to non‐pregnant control (p = 0.004) and pregnant control (p <0.001). Women with severe pre‐eclampsia had a significantly lower serum visfatin level than those with mild pre‐eclampsia (114.6±80.9 versus 425.2±122.1ng/ml, p = 0.037). Conclusions. A decrease in visfatin level was demonstrated in pre‐eclampsia, suggesting that visfatin and adipokine‐associated metabolic abnormalities are involved in the pathogenesis of the disease.

Alteration of peripheral CD4+CD25+ regulatory T lymphocytes in pregnancy and pre-eclampsia

Objectives. To clarify the change of peripheral CD4+CD25+ regulatory T lymphocytes in normal pregnancy and pre‐eclampsia and to explore its role in the pathogenesis of pre‐eclampsia. Methods. Twenty‐seven women with pre‐eclampsia, 27 with normal third trimester pregnancy and 27 healthy non‐pregnant women were recruited. Blood samples were taken and surface antigen CD4 and CD25 were labelled with fluorescence‐conjugated antibodies. CD4+CD25+ regulatory T cells were analysed by flow cytometry, and the proportion in T cells and the amount of regulatory T lymphocytes were calculated. Results. The amount and the proportion of regulatory T cells were not significantly different among non‐pregnant, normal pregnancy and pre‐eclampsia groups (p>0.05 for both). There were no significant differences in the proportion and the amount of CD4+CD25+ regulatory T cells between mild and severe pre‐eclampsia subgroups (p>0.05 for both). Conclusions. No significant change of peripheral regulatory T cells was observed in the current investigation, suggesting other mechanisms rather than CD4+CD25+ regulatory T cells were involved in the pathogenesis of pre‐eclampsia.

Elevated serum levels of interleukin-15 and interleukin-16 in preeclampsia

A generalized inflammatory response has been considered to be the main pathology and has an important role in the pathogenesis of preeclampsia. The immune aberrations per se and immunomodulatory milieu present in serum need to be elucidated. The purpose of the current investigation was to characterize changes in serum levels of interleukin (IL)-15 and IL-16 in preeclampsia. Thirty-seven women with preeclampsia were recruited and 36 age- and gestational age-matched women with normal pregnancy served as control. Levels of IL-15 and IL-16 were detected with immune assays in all serum samples. We found that serum levels of IL-15 and IL-16 were significantly higher in preeclampsia than in normal pregnancy (p<0.001 for both). There were significant differences in serum IL-15 and IL-16 between mild and severe preeclampsia (p<0.01 for both). Our data corroborate the hypothesis of an increased inflammatory response in preeclampsia, as illustrated by the elevated serum levels of IL-15 and IL-16, suggesting their possible role in the pathogenesis of preeclampsia. These associations may offer insight into the pathophysiology of preeclampsia.

Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy

ObjectivesTo investigate the alterations in gene profile of placenta from pregnant women with intrahepatic cholestasis of pregnancy (ICP) and to enhance the insight of etiology and pathogenesis of ICP.MethodsTen pregnant women diagnosed ICP were recruited and 10 healthy pregnant women served as control. Four samples were taken from each placenta and RNA was isolated. Gene expression was analyzed with microarray and real time PCR was used to validate the differentially expressed genes.Results392 genes were found differentially expressed. Among these differentially expressed genes, 280 were up-regulated and 112 were down-regulated. These differentially expressed genes involved 20 categories including genes involved in transportation, cell growth, apoptosis and immune response that were putatively participated the pathogenesis of ICP.Conclusions293 differentially expressed genes of 20 categories were found in ICP placenta, suggesting the diversity of gene expression alteration and the complexity of etiology and pathogenesis of ICP.

Increased serum levels of neopterin and soluble interleukin‐2 receptor in intrahepatic cholestasis of pregnancy

Objectives.  The etiology of intrahepatic cholestasis of pregnancy (ICP), a pregnancy‐specific complication, remains not completely understood. Some alterations of immunity in ICP were reported, but the profile of immune alteration was far from clarified. The aim of this investigation was to characterize the changes of serum levels of neopterin, a marker for the activation of macrophage, and soluble interleukin‐2 receptor (sIL‐2R), a marker for the activation of lymphocyte, in ICP.

Serum T helper 1‐ and 2‐type cytokines in preeclampsia

Preeclampsia is peculiar to human gestation and its etiology remains unclear [1]. The imbalance of T helper 1 (Th1) and Th2-type cytokines has been found in peripheral lymphocyte and placenta in preeclampsia and considered involved in the disease pathogenesis [2,3]. However, the balance of serum Th1/Th2 cytokines was rarely linked to preeclampsia [4]. This investigation was designed to determine the serum levels of IL-2, IL-10 and TNF-a and to observe the alterations in the balance of serum cytokines in preeclampsia and gestational hypertension. The subjects were 22 women with preeclampsia, 15 with gestational hypertension and 32 with normal term pregnancy. The diagnosis of preeclampsia and gestational hypertension was made according to the criteria recommended by ACOG.

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus

Background: Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission, but most of the infants born to HBV-positive mothers are protected from infection. However, the mechanisms by which intrauterine transmission is avoided remain elusive, and the roles of toll-like receptors (TLRs) have been proposed. The aims of this study were to clarify if TLR 7 and 8 are involved in the prevention of intrauterine transmission of HBV. Methods: Real time polymerase-chain reaction (PCR) was used to determine the expression of TLRs and cytokines in placenta and trophoblasts. The expression of MyD88 was interfered with small interfering RNA (siRNA) in trophoblasts. An in intro model mimicking trophoblast barrier was established to evaluate the effect of MyD88 siRNA on HBV transmission across trophoblast barrier. Results: There were significant differences in placental expression of TLR7 (F=3.263, P=0.048) and TLR8 (F=3.257, P=0.048) among control (HBV-negative women), non-infected group (HBV-positive women whose infants were not infected) and infected group (HBV-positive women whose infants were infected). The expression of TLR7 was significantly higher in non-infected group than infected group (P=0.039) and control (P=0.043). There was a significant difference in TLR8 expression between non-infected group and control (P=0.014), and the difference was close to but not significant (P=0.074) between non-infected and infected groups. Exposure of trophoblast to HBV significantly induced the expression of TLR7 (P<0.001), TLR8 (P=0.005), MyD88 (P=0.004), interferon (IFN)-α (P=0.004), IFN-β (P<0.001) and interleukin (IL)-8 (P=0.001). When MyD88 was interfered by siRNA, the expression of IFN-α (P<0.001), IFN-β (P=0.01) and IL-8 (P<0.001) was significantly decreased while the amount of HBV transcytosed across trophoblastic barrier significantly increased (P=0.03). Conclusions: TLR7 and TLR8 on trophoblastic cells play an important role in the prevention of intrauterine HBV transmission by inhibiting HBV translocation across trophoblast.

Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti‐microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β‐defensin‐3 (HBD‐3), apolipoprotein B mRNA‐editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV‐seronegative pregnant women (controls), 7 HBV‐seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV‐seropositive pregnant women with non‐infected infants (non‐infected group). The expression of HBD‐3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD‐3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD‐3 and A3G were higher in non‐infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD‐3, A3G, and MBL by Swan 71. It may be concluded HBV up‐regulates HBD‐3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up‐regulation is possibly associated with intrauterine transmission of HBV. J. Med. Virol. 87:375–379, 2015.

Impaired Mixed Lymphocyte Reaction in Intrahepatic Cholestasis of Pregnancy

Objective: To clarify the alteration of maternal-fetal mixed lymphocyte reaction (MLR) in intrahepatic cholestasis of pregnancy (ICP). Methods: Twenty-two patients with intrahepatic cholestasis of pregnancy and 21 normal pregnant women were recruited into the present study. Of patients with ICP, 5 also experienced pregnancy-induced hypertension (PIH). Maternal-fetal mixed lymphocyte reaction was conducted by using a morphologic transformation method, and the transformation rates of lymphocytes were compared either between ICP patients with and without pregnancy-induced hypertension, or between control and ICP group. Results: In the ICP group, the transformation rates of lymphocytes were not significantly different between pregnancies with and without pregnancy-induced hypertension (p > 0.5). Compared with control, the transformation rate of lymphocytes in intrahepatic cholestasis of pregnancy decreased significantly (p < 0.001). Conclusion: Suppressed mixed lymphocyte reaction was observed in intrahepatic cholestasis of pregnancy and its mechanism behind and role in the disease need to be further explored.