Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?
Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?
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DOI：
10.3389/fcimb.2021.694298
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发表时间：
2021
影响因子：
5.7
通讯作者：
Cheng S
中科院分区：
文献类型：
--
作者：
Banerjee S;Huang Z;Wang Z;Nakashima A;Saito S;Sharma S;Cheng S
对无菌性炎症及其相关生物学触发因素和疾病的认识仍处于初级阶段。在感染与病理学无关的情况下，这一点变得更加必要。细菌和病毒感染对母胎界面的免疫反应以及妊娠结局的不利影响已得到充分证实。然而，感染引起的病因并不被认为是严重妊娠并发症如先兆子痫（PE）和妊娠期糖尿病的主要促成因素。那么炎症信号如何被认为与这些妊娠并发症有关呢？目前尚不清楚PE样特征的发作涉及何种类型的炎症。我们认为炎症体-gasdermins-caspase-1轴调控的无菌性炎症是PE发病的一个促成因素。我们假设PE胎盘中损伤相关分子模式（DAMP）或Alarmins（如高迁移率族蛋白1（HMGB 1）、无细胞胎儿DNA、尿酸、NOD样受体含芘受体3（NLRP 3）炎性体、IL-1β和IL-18）的产生和释放增加。其中一些分子已经在PE女性的胎盘中观察到。从机制上讲，新出现的证据表明，过度的胎盘内质网（ER）应激、受损的自噬和GSDMD介导的内源性焦亡是导致PE患者（尤其是早发性PE（e-PE））全身性无菌性炎症的关键事件。在这篇综述中，我们重点介绍了无菌炎症和炎症信号级联反应在PE病理生理学中的作用，包括ER应激、自噬缺陷和焦亡。破译这些炎症通路的机制可能提供潜在的诊断生物标志物，并促进治疗这种毁灭性疾病的治疗策略的发展。
Understanding of sterile inflammation and its associated biological triggers and diseases is still at the elementary stage. This becomes more warranted in cases where infections are not associated with the pathology. Detrimental effects of bacterial and viral infections on the immune responses at the maternal-fetal interface as well as pregnancy outcomes have been well documented. However, an infection-induced etiology is not thought to be a major contributing component to severe pregnancy complications such as preeclampsia (PE) and gestational diabetes. How is then an inflammatory signal thought to be associated with these pregnancy complications? It is not clear what type of inflammation is involved in the onset of PE-like features. We opine that sterile inflammation regulated by the inflammasome-gasdermins-caspase-1 axis is a contributory factor to the onset of PE. We hypothesize that increased production and release of damage-associated molecular patterns (DAMPs) or Alarmins such as high-mobility group box1 (HMGB1), cell-free fetal DNA, uric acid, the NOD-like receptor pyrin-containing receptor 3 (NLRP3) inflammasome, IL-1β and IL-18 occur in the PE placenta. Some of these molecules have already been observed in the placenta from women with PE. Mechanistically, emerging evidence has demonstrated that excessive placental endoplasmic reticulum (ER) stress, impaired autophagy and gasdermine D (GSDMD)-mediated intrinsic pyroptosis are key events that contribute to systemic sterile inflammation in patients with PE, especially early-onset PE (e-PE). In this review, we highlight the advances on the roles of sterile inflammation and inflammatory signaling cascades involving ER stress, autophagy deficiency and pyroptosis in PE pathophysiology. Deciphering the mechanisms underlying these inflammatory pathways may provide potential diagnostic biomarkers and facilitate the development of therapeutic strategies to treat this devastating disease.