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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Inflammasome components and ADAMTS4 in premature rupture of membranes
Jinming Zhu1, Chunling Ma2, Xiaomei Luan1
1Department of Obstetrics, Xuzhou Maternity and Child Health Care Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221009, P.R. China.
Abstract:
Inflammation may be responsible for the development of premature rupture of membranes (PROM) including preterm PROM (PPROM) and mature PROM (MPROM). A total of four classic receptor proteins have been confirmed to assemble inflammasomes: NLR family pyrin domain containing (NLRP)1, NLRP3 and NLR family CARD‑domain containing 4 (NLRC4) and absent in melanoma 2 (AIM2). The activation and expression of these receptor‑modulated inflammasomes in placenta and fetal membrane of PROM pregnancies requires investigation. In addition, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a risk factor for PROM, but whether its expression is associated with inflammasome activation remains to be elucidated. In the present study, the placenta and fetal membrane tissues of patients who had suffered PPROM and MPROM and healthy pregnancies were investigated. Reverse transcription‑quantitative PCR was used to determine the mRNA expression of inflammasomes and ADAMTS4. Western blotting, immunohistochemistry and ELISA were used to investigate the protein expression levels of inflammasomes and ADAMTS4. The results demonstrated that all four inflammasomes were elevated in placenta and fetal membrane of PPROMs as were mRNA and protein expression levels of IL‑18 and IL‑1β (compared with controls). A further increase of inflammasomes and interleukins was observed in MPROMs compared with controls. Similar results were also observed in ADAMTS4 expression in PPROM and MPROM groups. However, immunohistochemistry results revealed no significant difference of inflammasome receptor expression in PPROMs compared with controls. Finally, a general positive correlation between ADAMTS4 and all four inflammasome receptors in placenta and fetal membrane of PPROMs and MPROMs was observed. The present study revealed that NLRP1, NLRP3, AIM2 and NLRC4 inflammasome activation in PROM was increased. Promoted ADAMTS4 level was further observed in PROM group and was significantly correlated with inflammasome expression. Inhibition of inflammasome activation may provide a therapeutic target for clinical PROM treatment.
Insights
Inflammation drives premature rupture of membranes (PROM). Key inflammasome receptors (NLRP1, NLRP3, NLRC4, AIM2) and ADAMTS4 are elevated in PROM, suggesting therapeutic targets.
Area of Science:
- Obstetrics and Gynecology
- Immunology
- Molecular Biology
Background:
- Inflammation is implicated in premature rupture of membranes (PROM), a condition affecting both preterm PROM (PPROM) and mature PROM (MPROM).
- Four key inflammasome receptor proteins (NLRP1, NLRP3, NLRC4, AIM2) are known to mediate inflammatory responses.
- The role of these inflammasomes and ADAMTS4 in PROM pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the activation and expression of inflammasome receptors (NLRP1, NLRP3, NLRC4, AIM2) and ADAMTS4 in the placenta and fetal membranes of pregnancies with PPROM and MPROM.
- To determine the correlation between inflammasome activation and ADAMTS4 expression in PROM.
Main Methods:
- Analysis of placenta and fetal membrane tissues from PPROM, MPROM, and control pregnancies.
- Reverse transcription-quantitative PCR (RT-qPCR) to assess mRNA expression of inflammasomes and ADAMTS4.
- Western blotting, immunohistochemistry, and ELISA to evaluate protein expression levels of inflammasomes and ADAMTS4.
Main Results:
- Elevated mRNA and protein levels of all four inflammasomes (NLRP1, NLRP3, NLRC4, AIM2) and associated interleukins (IL-1β, IL-18) were observed in PPROM and MPROM tissues compared to controls.
- ADAMTS4 expression was also significantly increased in PROM groups.
- A positive correlation was found between ADAMTS4 expression and the four inflammasome receptors in PROM cases.
Conclusions:
- Inflammasome activation, involving NLRP1, NLRP3, NLRC4, and AIM2, is significantly increased in PROM.
- Elevated ADAMTS4 levels are associated with inflammasome activation in PROM.
- Targeting inflammasome activation presents a potential therapeutic strategy for managing PROM.
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