Abstract
We investigated whether there was activation of NLRP1 inflammasomes and excessive autophagy in oxidative stress damage. And we further demonstrate whether there is a cascade relationship between the activation of NLRP1 inflammasomes and the phenomenon of excessive autophagy. To observe the expression level of the NLRP1 inflammasome group in the pathological process of trophoblast cell oxidative stress, western blot, immunofluorescence, and qRT-PCR were performed. Autophagy in trophoblast cells after the action of H2O2 was detected by using normal trophoblast cells' NLRP1-specific activator (MDP) as a positive control. The presence of excessive autophagy was determined by comparing it with the autophagy-related proteins in normal trophoblast cells. Through siRNA-NLRP1, we investigated the role of oxidative stress and the NLRP1 inflammasome in autophagy in cells. 100 μmol MDP for 24 hours can be used as the optimal concentration of the NLRP1 activator. In human placental trophoblast oxidative stress, the model group significantly increased the expression level of inflammasome IL-1β, CASP1, and NLRP1, compared with the control group NLRP3, and LC3-II, Beclin-1, ATG5, ATG7, and p62 overactivated the autophagy ability of cells. After the activation of NLRP1, the expression of these inflammasomes increased, accompanied by the decrease in autophagy. After the expression of NLRP1 was silenced by RNAi, the expression of inflammasome IL-1β, CASP1, and NLRP3 was also decreased. Still, the autophagy level was increased, which was manifested by the high expression of LC3-II, Beclin-1, ATG5, and ATG7 and the decrease in p62. Trophoblast cells showed the expression of NLRP1 protein and excessive autophagy under oxidative stress. Simultaneously, the NLRP1 inflammasome of trophoblast cells in the state of oxidative stress was correlated with autophagy. Inflammasome activation and autophagy were shown to be linked and to influence each other mutually. These may also provide new therapeutic targets in a pathological pregnancy.
Highlights
IntroductionThe balance of anti-inflammatory and proinflammatory at the maternal-fetal interface plays an essential role in maintaining pregnancy
Pregnancy is considered a kind of allotransplantation process
The results showed that the expression of NLRP1 and NLRP3 in the oxidative stress model of HTR-8/SVneo cells treated with H2O2 was significantly increased (P < 0:01)
Summary
The balance of anti-inflammatory and proinflammatory at the maternal-fetal interface plays an essential role in maintaining pregnancy. The presence of excessive amounts of ROS can damage the lipids, proteins, or DNA of cells, thereby inhibiting their normal function [2]. Oxidative stress is related to many human diseases. There is increasing evidence that oxidative stress is closely related to the occurrence of pathological pregnancy outcomes such as abortion and preeclampsia [3]. The body’s oxidation and antioxidant functions are relatively balanced during a normal pregnancy, and no oxidative stress is present [4]. The oxidative damage of human trophoblasts caused by any mechanism will lead to decreases in proliferation and invasiveness, abnormal placenta formation and development, and a pathological pregnancy [5]
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