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NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

  • Authors:
    • Wei Wu
    • Qing-Ying Tan
    • Fang-Fang Xi
    • Yun Ruan
    • Jing Wang
    • Qiong Luo
    • Xiao-Bing Dou
    • Tian-Xiao Hu
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China, Department of Endocrinology, Chinese PLA 903rd Hospital (Former Chinese PLA 117th Hospital), Hangzhou, Zhejiang 310013, P.R. China, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 94
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    Published online on: November 30, 2021
       https://doi.org/10.3892/etm.2021.11017
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Abstract

The placenta may play a key role in the activation of inflammation and initiation of insulin resistance (IR) during gestational diabetes mellitus (GDM) pathogenesis. Interleukin (IL)‑1β and IL‑18, regulated by NLR family pyrin domain containing‑3 (NLRP3) inflammasome, are important inflammatory cytokines in the initiation of maternal IR during GDM. However, the mechanism responsible for the regulatory of NLRP3 inflammasome in placenta remains unknown. Hydrogen sulfide (H2S) exerts anti‑inflammatory function partially via suppressing the activation of the NLPR3 inflammasome. The present study aimed to investigate the role of NLRP3 inflammasome, H2S synthetase cystathionine‑γ‑lyase (CSE) and cystathionine‑β‑synthetase (CBS) in placenta in the pathogenesis of GDM. Clinical placenta samples were collected from pregnant women with GDM (n=16) and healthy pregnant women at term (n=16). Western blot analysis was performed to detect the protein expression levels of NLRP3, cleaved caspase‑1, CBS and CSE in the placenta samples. Pearson's correlation analysis was performed to assess the correlation between NLRP3 inflammasome and H2S synthetase. Human placental cells were cultured and treated with different concentrations of NaHS (0, 10, 25 and 50 nmol/l) or L‑cysteine (0, 0.25, 0.50 and 1.00 mmol/l). In addition, western blot analysis was performed to detect the protein expression levels of NLRP3 and cleaved caspase‑1, while ELISA was performed to measure the production of IL‑1β and IL‑18 in the culture media. The results demonstrated that the expression levels of NLRP3 and cleaved caspase‑1 increased, while the expression levels of CBS and CSE decreased in the placenta samples. In addition, the expression levels of NLRP3 and cleaved caspase‑1 were inversely correlated with the expression levels of CBS and CSE. Notably, NaHS and L‑cysteine significantly suppressed the expression levels of NLRP3 and cleaved caspase‑1, and the production of IL‑1 and IL‑18 in human placental cells. Taken together, the results of the present study suggest that H2S synthetase deficiency in placenta may contribute to excessive activation of NLRP3 inflammasome in GDM.
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Spandidos Publications style
Wu W, Tan Q, Xi F, Ruan Y, Wang J, Luo Q, Dou X and Hu T: NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency. Exp Ther Med 23: 94, 2022.
APA
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q. ... Hu, T. (2022). NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency. Experimental and Therapeutic Medicine, 23, 94. https://doi.org/10.3892/etm.2021.11017
MLA
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q., Dou, X., Hu, T."NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency". Experimental and Therapeutic Medicine 23.1 (2022): 94.
Chicago
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q., Dou, X., Hu, T."NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency". Experimental and Therapeutic Medicine 23, no. 1 (2022): 94. https://doi.org/10.3892/etm.2021.11017
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Spandidos Publications style
Wu W, Tan Q, Xi F, Ruan Y, Wang J, Luo Q, Dou X and Hu T: NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency. Exp Ther Med 23: 94, 2022.
APA
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q. ... Hu, T. (2022). NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency. Experimental and Therapeutic Medicine, 23, 94. https://doi.org/10.3892/etm.2021.11017
MLA
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q., Dou, X., Hu, T."NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency". Experimental and Therapeutic Medicine 23.1 (2022): 94.
Chicago
Wu, W., Tan, Q., Xi, F., Ruan, Y., Wang, J., Luo, Q., Dou, X., Hu, T."NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency". Experimental and Therapeutic Medicine 23, no. 1 (2022): 94. https://doi.org/10.3892/etm.2021.11017
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