Amniotic Fluid Proteasome and Immunoproteasome in the Setting of Intra-Amniotic Infection, Inflammation, and Preterm Birth.
Amniotic Fluid Proteasome and Immunoproteasome in the Setting of Intra-Amniotic Infection, Inflammation, and Preterm Birth.
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DOI：
10.1007/s43032-021-00512-7
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Buhimschi IA
中科院分区：
文献类型：
--
作者：
Ware CA;Buhimschi CS;Zhao G;El Helou Y;Buhimschi IA
早产是新生儿发病率和死亡率的重要决定因素，羊膜内感染（IAI）和炎症起着致病作用。组成性蛋白酶体和免疫蛋白酶体是维持蛋白质稳态的关键因素，它们在妊娠外的改变与许多炎症性疾病的发病机制有关。本研究的目的是探讨感染和/或炎症引起的早产妇女羊水蛋白酶体的水平、活性及其可能的来源。对155名孕妇经腹穿刺取出的房颤患者进行了总蛋白酶体和免疫蛋白酶体浓度测定。用靶向半胱天冬酶样（CAS-L）、胰蛋白酶样（TRY-L）或化学胰蛋白酶样（CHE-L）裂解活性的荧光底物测量蛋白酶体活性。我们发现IAI显著上调AF总蛋白酶体和免疫蛋白酶体的浓度（两者均P<0.001），且基于胎龄无差异。基于底物的偏好和药理学抑制的概况，我们确定了CHE-L活性的免疫蛋白酶体作为主要的溶解活性上调AF的妊娠并发IAI。与匹配的母血和脐带血相比，AF中蛋白酶体活性最高，IAI中蛋白酶体活性进一步升高。Western blot证实了组成性蛋白酶体和免疫蛋白酶体的β5（PSMB 5）和β5i（PSMB 8）亚基存在于AF中，并指出绒毛-蜕膜是AF的潜在来源。总之，IAI与AF免疫蛋白酶体活性增加相关，与其他炎症性疾病类似，AF免疫蛋白酶体活性增加可能产生抗原性寡肽，并可能在触发早产中发挥作用。
Preterm birth is an important determinant of neonatal morbidity and mortality and intra-amniotic infection (IAI) and inflammation play a causative role. The constitutive proteasome and immunoproteasome are key players in maintenance of proteostasis and their alteration outside pregnancy has been linked to pathogenesis of numerous inflammatory diseases. Our goal was to evaluate the levels, activities and potential origin of amniotic fluid (AF) proteasome in women with preterm birth induced by infection and/or inflammation. Total proteasome and immunoproteasome concentrations were measured in AF retrieved by trans-abdominal amniocentesis from 155 pregnant women. Proteasome activities were measured with fluorogenic substrates targeting caspase-like (CAS-L), trypsin-like (TRY-L) or chemotrypsin-like (CHE-L) lytic activities. We found that IAI significantly upregulated AF concentrations of total proteasome and of the immunoproteasome (P<.001 for both) with no differences based on gestational age. Based on substrate preference and profile of pharmacologic inhibition, we identified the CHE-L activity of the immunoproteasome as the primary lytic activity upregulated in AF of pregnancies complicated by IAI. When compared with matched maternal blood and cord blood, proteasome activity was by far the highest in AF and this was further elevated in IAI. Western blot confirmed β5 (PSMB5) and β5i (PSMB8) subunits of the constitutive proteasome and immunoproteasome are present in AF and IHC staining of fetal membranes pointed to chorio-decidua as a potential source. In conclusion, IAI is associated with increased AF immunoproteasome activity that by analogy with other inflammatory diseases may generate antigenic oligopeptides and may play a role in triggering preterm birth.
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DOI：
10.1084/jem.183.4.1807
发表时间：
1996-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hisamatsu H;Shimbara N;Saito Y;Kristensen P;Hendil KB;Fujiwara T;Takahashi E;Tanahashi N;Tamura T;Ichihara A;Tanaka K
通讯作者：
Tanaka K
影响因子：
82.9
作者：
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通讯作者：
Groettrup, Marcus
影响因子：
3.8
作者：
Loukissa, A;Cardozo, C;Nelson, JE
通讯作者：
Nelson, JE
影响因子：
7.2
作者：
通讯作者：
--
影响因子：
4.4
作者：
Khan, S;van den Broek, M;Groettrup, M
通讯作者：
Groettrup, M