Pyroptosis and inflammasomes in obstetrical and gynecological diseases.

Pyroptosis, an inflammatory form of programmed cell death, takes an essential part in a wide variety of physiological activities, for instance, implantation, placentation and the body's defense against infection. However, once excessively activated, pyroptosis mediated by the activation of inflammasomes can be highly pathological. It can cause inflammatory and autoimmune diseases including a variety of obstetrical and gynecological diseases, such as endometriosis, gestational diabetes mellitus, insulin resistance in polycystic ovary syndrome, and multiple obstetric complications including preeclampsia. Although the role of pyroptosis in the pathogenesis of the above mentioned diseases has not been fully elucidated, we try to tap its therapeutic potential by targeting pyroptosis signaling and inflammasome formation. Pyroptosis and inflammasomes are confirmed to be involved in endometriosis and gynecological malignant tumors, therefore, medical approachs inducing pyroptosis of the ectopic endometrium and tumor cells can be feasible treatments for endometriosis and gynecological cancers. On the maternal-fetal interface, although a certain level of the innate immune response activation is required for a successful implantation and placentation, maternal and fetal injury may occur once the inflammasomes are over-activated. Besides, since gestational diabetes mellitus and insulin resistance in polycystic ovary syndrome share common pathogenesis with metabolic diseases, this domain research sheds light on future study of some obstetrical and gynecological diseases.

Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease.

BACKGROUND: Emerging evidence indicates that inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Several proteins including α-synuclein trigger the activation of NLRP3 inflammasome. However, few studies examined whether inflammasomes are activated in the periphery of PD patients and their possible value in the diagnosis or tracking of the progress of PD. The aim of this study was to determine the association between inflammasome-induced inflammation and clinical features in PD. METHODS: There were a total of 67 participants, including 43 patients with PD and 24 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including Hoehn and Yahr (H-Y) staging scale. Blood samples were collected from all participants. The protein and mRNA expression levels of inflammasomes subtypes and components in peripheral blood mononuclear cells (PBMCs) were determined using western blotting and RT-qPCR. We applied Meso Scale Discovery (MSD) immunoassay to measure the plasma levels of IL-1ß and α-synuclein. RESULTS: We observed increased gene expression of NLRP3, ASC, and caspase-1 in PBMCs, and increased protein levels of NLRP3, caspase-1, and IL-1ß in PD patients. Plasma levels of IL-1ß were significantly higher in patients with PD compared with controls and have a positive correlation with H-Y stage and UPDRS part III scores. Furthermore, plasma α-synuclein levels were also increased in PD patients and have a positive correlation with both UPDRS part III scores and plasma IL-1ß levels. CONCLUSIONS: Our data demonstrated that the NLRP3 inflammasome is activated in the PBMCs from PD patients. The related inflammatory cytokine IL-1ß and total α-synuclein in plasma were increased in PD patients than controls, and both of them presented a positive correlation with motor severity in patients with PD. Furthermore, plasma α-synuclein levels have a positive correlation with IL-1ß levels in PD patients. All these findings suggested that the NLRP3 inflammasome activation-related cytokine IL-1ß and α-synuclein could serve as non-invasive biomarkers to monitor the severity and progression of PD in regard to motor function.