Identification of interleukin‐1 beta, but no other inflammatory proteins, as an early onset pre‐eclampsia biomarker in first trimester serum by bead‐based multiplexed immunoassays

Siljee, Jacqueline E.; Wortelboer, E. J.; Köster, Maria; Imholz, Sandra; Rodenburg, Wendy; Visser, Gerard H.A.; Vries, Annemieke de; Schielen, Peter C. J. I.; Pennings, Jeroen L. A.

doi:10.1002/pd.4219

Cited by 40 publications

(25 citation statements)

References 40 publications

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“…IL-1b, a key inflammatory factor, is highly expressed in PE patients [36,37,44]. In this study, we found that miR-30a could regulate the immunosuppressive function of IL-1b-elicited MSCs.…”

Section: Discussionmentioning

confidence: 61%

“…IL-1b, a crucial soluble inflammatory mediator, can enhance the immunosuppressive functions of MSCs and induce their production of IL-6, COX2 and IL-8 [34,35]. Importantly, the up-regulation of IL-1b expression was observed in PE patients [36,37]. To investigate the effects of miR-30a on the immunoregulatory activities of MSCs, IL-1b was used to stimulate the transfected MSCs.…”

Section: Over-expressed Mir-30a Suppresses the Immunosuppressive Actimentioning

confidence: 99%

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MiR‐30a attenuates immunosuppressive functions of IL‐1β‐elicited mesenchymal stem cells via targeting TAB3

Ding

Miao

et al. 2015

FEBS Letters

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a b s t r a c tMesenchymal stem cells (MSCs) possess the ability to modulate the immune response, and their abnormalities are related to several diseases. We previously reported that miR-30a expression significantly increased in the maternal-fetal interface during preeclampsia (PE), but the effects of miR-30a on the immunoregulatory characteristics of MSCs are unclear. In this study, we determined that miR-30a over-expression inhibited the IL-1b-elicited activation of the nuclear factor jB (NF-jB) and JNK signaling pathways and the production of IL-6, cyclooxygenase 2 (COX2) and IL-8 by targeting transforming growth factor-b-activated kinase 1 binding protein 3 (TAB3) in MSCs. Moreover, the over-expression of miR-30a also impaired MSCs' anti-inflammatory effects on macrophages. These data demonstrated that miR-30a in MSCs may participate in the immune dysregulation of the maternal-fetal interface during PE.

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“…IL-1b, a key inflammatory factor, is highly expressed in PE patients [36,37,44]. In this study, we found that miR-30a could regulate the immunosuppressive function of IL-1b-elicited MSCs.…”

Section: Discussionmentioning

confidence: 61%

Section: Over-expressed Mir-30a Suppresses the Immunosuppressive Actimentioning

confidence: 99%

MiR‐30a attenuates immunosuppressive functions of IL‐1β‐elicited mesenchymal stem cells via targeting TAB3

Ding

Miao

et al. 2015

FEBS Letters

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“…A limitation of this study is the relatively small number of cases, but we find these numbers to be comparable to previous casecontrol studies investigating serum cytokines in hypertensive pregnancy disorders, 33,34,53 and our study includes a larger control group. Because our medium-to high-risk cohort predominantly included women developing late-onset gestational hypertension or preeclampsia, the findings presented here should be followed-up in a general pregnant population with larger groups, including early-and late-onset disease.…”

Section: Downloaded Frommentioning

confidence: 78%

“…28,29 A first trimester study by Wolf et al concluded that inflammatory activation, assessed by high-sensitivity C-reactive protein measurements, was not associated with gestational hypertension, 44 but our somewhat contradictory findings result from a more comprehensive cytokine profiling approach. For preeclampsia, serum cytokine profiling has previously shown results ranging from elevated first trimester IL-1β levels predicting early onset disease 34 to no cytokine differences before clinical manifestation of early or late onset preeclampsia. 45,46 We did not find any such differences in our cohort of late onset preeclampsia compared with normotensive pregnancies.…”

Section: Downloaded Frommentioning

confidence: 99%

“…[27][28][29][30][31][32] Information is limited for early pregnancy; serum IL-1β and TNF-α has been shown elevated before onset of disease in women developing preeclampsia, whereas gestational hypertension has not been separately investigated at early gestation. 33,34 This study aimed to compare disease-specific early gestation serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia.…”

Section: Tangerås Et Al Cytokines In Hypertensive Pregnancy Disordersmentioning

confidence: 99%

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Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Tangerås

Austdal

Skråstad

et al. 2015

ATVB

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Objective-Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. Approach and Results-The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11 0 -13 6 were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. Conclusions-This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia.

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Endoplasmic reticulum stress may activate NLRP3 inflammasomes via TXNIP in preeclampsia

Yang

Han

et al. 2019

Cell Tissue Res

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Preeclampsia (PE) development is often associated with placental immune and inflammatory dysregulation, as well as endoplasmic reticulum (ER) stress. However, the mechanisms linking ER stress and inflammatory dysregulation to PE have not been clarified. It has been reported that thioredoxin-interacting protein (TXNIP), which can bind with and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome, plays a critical role in immune regulation. Recent experimental evidence suggests that activated NLRP3 inflammasomes can activate interleukin-1β (IL-1β) production in the placenta of patients with PE. The objective of the current study was to explore if TXNIP plays a critical signaling role linking ER stress with NLRP3 inflammasome activation in PE. We hypothesised that ER stress would induce TXNIP production, which would bind with NLRP3 inflammasomes to activate IL-1β production. HTR8/SVneo cells were subjected to six hours hypoxia followed by six hours reoxygenation (H/R). These cells showed a higher protein level of NLRP3 and IL-1β, as well as a higher enzymatic activity of caspase-1, indicating enhanced inflammatory dysregulation and ER stress. Cells transfected with TXNIP siRNA showed reduced NLRP3 inflammasome activation. Cells treated with 4-phenylbutyric acid, an inhibitor of ER stress, showed a similar result. In addition, the outgrowth of explant with TXNIP lentivirus in H/R or Tunicamycin (inducers of ER stress) was also measured to verify our hypothesis. These findings demonstrated that TXNIP could influence inflammatory dysregulation by mediating ER stress and NLRP3 inflammasome activation in PE. This novel mechanism may further explain the inflammation observed at the maternal-fetal interface, which leads to placental dysfunction in a patient with PE.

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Identification of interleukin‐1 beta, but no other inflammatory proteins, as an early onset pre‐eclampsia biomarker in first trimester serum by bead‐based multiplexed immunoassays

Abstract: This study indicates that IL-1β has potential to improve first trimester prediction of pre-eclampsia. Studies on larger cohorts will be needed to validate these findings.

Cited by 40 publications

References 40 publications

MiR‐30a attenuates immunosuppressive functions of IL‐1β‐elicited mesenchymal stem cells via targeting TAB3

MiR‐30a attenuates immunosuppressive functions of IL‐1β‐elicited mesenchymal stem cells via targeting TAB3

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Endoplasmic reticulum stress may activate NLRP3 inflammasomes via TXNIP in preeclampsia

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