Hydrogen Sulfide Contributes to Uterine Quiescence Through Inhibition of NLRP3 Inflammasome Activation by Suppressing the TLR4/NF-κB Signalling Pathway
Zixi Chen,1,* Mengzhe Zhang,1,* Yunzhi Zhao,2 Wenjuan Xu,2 Fenfen Xiang,1 Xiaoxiao Li,1 Tao Zhang,1 Rong Wu,1 Xiangdong Kang1 1Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of...
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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/9b63c6c97b5645cca555006b71e49047 |
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| Sumario: | Zixi Chen,1,* Mengzhe Zhang,1,* Yunzhi Zhao,2 Wenjuan Xu,2 Fenfen Xiang,1 Xiaoxiao Li,1 Tao Zhang,1 Rong Wu,1 Xiangdong Kang1 1Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangdong Kang; Rong WuDepartment of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai Email xd_kang@163.com; rong701@126.comBackground: The NLRP3 inflammasome plays a critical role in inflammatory responses in various diseases. Our previous study showed that NLRP3 expression was significantly increased in human pregnancy tissue during term labour. Therefore, we explored whether NLRP3 participated in inflammatory responses of preterm and term labour and whether this process could be relieved by H2S, one anti-inflammatory gasotransmitter.Methods: Human myometrium was obtained from non-labouring and labouring women. Mouse myometrium was obtained from LPS-induced infectious preterm labour. Uterine smooth muscle cells were isolated from non-labouring women’s myometrial tissues, transfected with siRNA, and treated cells with IL-1β, H2S donor NaHS, NF-κB inhibitor BAY 11– 7082 and TLR4 inhibitorTAK-242. The NLRP3 inflammasome, CSE, CBS, TLR4, uterine contraction-associated proteins (CAPs), NF-κB activation and inflammatory cytokine expression were assessed by Western blotting and RT-PCR.Results: The NLRP3 inflammasome, TLR4 and activated NF-κB expression were upregulated in human term labour, mouse preterm labour and human uterine smooth muscle cells treated with IL-1β. NLRP3 levels were negatively correlated with CSE and CBS expression. Treatment with the H2S donor NaHS delayed LPS-induced preterm birth in mice and inhibited NLRP3 inflammasome activation. In siNLRP3-transfected cells, there was a significant decrease in the expression of CAPs and inflammatory cytokines compared with IL-1β stimulation. In addition, treatment with the H2S donor NaHS inhibited NLRP3 inflammasome activation, reduced the expression of uterine contraction-associated proteins and inflammatory cytokines and reduced the activation of TLR4 and NF-κB compared with stimulation with IL-1β in human uterine smooth muscle cells. Furthermore, treatment of uterine smooth muscle cells with BAY 11– 7082 and TAK-242 found that NLRP3 activation was regulated by the TLR4 and NF-κB pathways.Conclusion: H2S suppresses CAP expression and the inflammatory response and contributes to uterine quiescence by inhibiting the TLR4/NF-κB signalling pathway and downstream NLRP3 inflammasome activation. Thus, H2S contributes to uterine quiescence through inhibition of NLRP3 inflammasome activation by suppressing the TLR4/NF-κB signalling pathway.Keywords: hydrogen sulfide, uterine quiescence, NLRP3 inflammasome, inflammation, TLR4/NF-κB |
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