Hypoxia and oxidative stress induce sterile placental inflammation in vitro.
Hypoxia and oxidative stress induce sterile placental inflammation in vitro.
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DOI：
10.1038/s41598-021-86268-1
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发表时间：
2021-03-31
影响因子：
4.6
通讯作者：
Jones RL
中科院分区：
文献类型：
--
作者：
Baker BC;Heazell AEP;Sibley C;Wright R;Bischof H;Beards F;Guevara T;Girard S;Jones RL
胎儿生长受限（FGR）和死胎与胎盘功能障碍有关，炎症和缺氧、氧化和硝化应激与胎盘损伤有关。损伤相关分子模式（DAMP）在FGR和死胎风险增加的妊娠中升高，并与促炎性胎盘细胞因子的增加相关。我们假设胎盘损伤导致DAMP的释放，促进胎盘炎症。将无并发症妊娠的胎盘组织在体外暴露于缺氧、氧化或硝化应激。测定DAMP和细胞因子的组织产生和释放。氧化应激和缺氧引起DAMPs的差异释放，包括尿酸，HMGB 1，S100 A8，游离胎儿DNA，S100 A12和HSP 70。氧化应激后，促炎细胞因子（IL-1α，IL-1β，IL-6，IL-8，TNFα，CCL 2）在外植体和条件培养基中均增加。缺氧可增加组织中IL-1α/β、IL-6、IL-8和TNFα的水平，以及IL-1α、IL-6和IL-8的释放，而CCL 2和IL-10则减少。IL 1受体拮抗剂（IL 1 Ra）治疗防止缺氧和氧化应激诱导的IL-6和IL-8的释放。这些发现提供了相关应激源在胎盘组织中诱导无菌炎症特征的证据，其可以被IL 1 Ra部分阻断，表明该试剂具有预防FGR和死胎中明显的胎盘炎症的转化潜力。
Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.
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DOI：
10.4049/jimmunol.1601179
发表时间：
2017-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brien ME;Duval C;Palacios J;Boufaied I;Hudon-Thibeault AA;Nadeau-Vallée M;Vaillancourt C;Sibley CP;Abrahams VM;Jones RL;Girard S
通讯作者：
Girard S
影响因子：
3.8
作者：
Christian, Lisa M.;Porter, Kyle
通讯作者：
Porter, Kyle
核因子-kappa B、p38 和应激激活蛋白激酶丝裂原激活蛋白激酶信号通路调节人胎盘外植体中的促炎细胞因子和细胞凋亡，以响应氧化应激：抗氧化维生素的作用。
影响因子：
6
作者：
Cindrova-Davies, Tereza;Spasic-Boskovic, Olivera;Jauniaux, Eric;Charnock-Jones, D. Stephen;Burton, Graham J.
通讯作者：
Burton, Graham J.
DOI：
10.1111/aji.12274
发表时间：
2014-10
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Girard S;Heazell AE;Derricott H;Allan SM;Sibley CP;Abrahams VM;Jones RL
通讯作者：
Jones RL
影响因子：
3.7
作者：
Díaz P;Sibley CP;Greenwood SL
通讯作者：
Greenwood SL