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Endoplasmic reticulum stress may activate NLRP3 inflammasomes via TXNIP in preeclampsia

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journal contribution
posted on 22.11.2019, 17:14 by Yong Yang, Jianxin Li, Ting-Li Han, Xianbo Zhou, Hongbo Qi, Philip N. Baker, Wei Zhou, Hua Zhang
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 elucidated. It has been reported that thioredoxin-interacting protein (TXNIP), which can bind with and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome, is a key point 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 hypothesized that ER stress would induce TXNIP production, which would bind with NLRP3 inflammasomes to activate IL-1β production. 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. Outgrowth of the 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.

Funding

This work was supported by the National Natural Science Foundation of China (No.81571453, 81771607, 81871185, 81701477), The 111 Project (Yuwaizhuan (2016)32), The National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention (2016YFC1000407), Chongqing Health Commission (2017ZDXM008,2018ZDXM024), and Chongqing Science & Technology Commission (cstc2017jcyjBX0062).

History

Citation

Yang, Y., Li, J., Han, TL. et al. Cell Tissue Res (2019). https://doi.org/10.1007/s00441-019-03104-9

Author affiliation

College of Medicine, Biological Sciences and Psychology

Version

AM (Accepted Manuscript)

Published in

Cell and Tissue Research

Publisher

Springer Berlin Heidelberg

issn

0302-766X

eissn

1432-0878

Acceptance date

20/08/2019

Copyright date

2019

Available date

22/11/2019

Publisher version

https://link.springer.com/article/10.1007/s00441-019-03104-9#enumeration

Notes

CRIS Deposit 01/11/2019 TM Correction to: Cell and Tissue Research (Published online: 22 October 2019) The authors apologize that in our published paper entitled “Endoplasmic reticulum stress may activate NLRP3 inflammasomes via TXNIP in preeclampsia”Cell and Tissue Research (Published online: 22 October 2019); The authorship and affiliation have the following errors. 1) The first author also belongs to Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University; 2) Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, should be listed as first in the affiliation.

Language

en