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凝集素在人胎盘中的差异表达及其在自然分娩时炎症中的作用。

Differential expression of collectins in human placenta and role in inflammation during spontaneous labor.

作者信息

Yadav Ajit Kumar, Chaudhari Hemangi, Warke Himangi, Shah Premanand Keshavlal, Dodagatta-Marri Eswari, Kishore Uday, Madan Taruna

机构信息

Department of Innate Immunity, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Mumbai, Maharashtra, India.

Department of Obstetrics and Gynecology, Seth Gordhandas Sunderdas Medical College and King Edward Medical (KEM) Hospital, Mumbai, Maharashtra, India.

出版信息

PLoS One. 2014 Oct 10;9(10):e108815. doi: 10.1371/journal.pone.0108815. eCollection 2014.

Abstract

Collectins, collagen-containing Ca(2+) dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥ 37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (p<0.05). In addition, the MMP-9-cleaved form of SP-D (25 kDa) was significantly higher in the placentae of 'SLv' group compared to the 'NLc' group (p = 0.002). Labor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (p<0.05) in a dose dependent manner in the placental explants treated with nSP-D and rhSP-D. In conclusion, the study emphasizes that SP-A and SP-D proteins associate with the spontaneous labor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.

摘要

凝集素是一类含胶原蛋白的、依赖钙离子的C型凝集素,是包括SP-A、SP-D和MBL在内的一类分泌蛋白,对免疫调节和先天性免疫防御至关重要。在本研究中,我们旨在研究它们在胎盘的转录合成、与分娩相关的差异表达及其在母胎界面的定位,以及它们在自然分娩中的功能意义。该研究使用了两组足月(≥37周妊娠)健康孕妇的母胎界面(胎盘/蜕膜组织),一组为择期剖宫产未临产(“NLc”组,n = 5),另一组为自然阴道分娩(“SLv”组,n = 5)。使用多重细胞因子阵列分析了足月胎盘外植体上SP-D的免疫功能,以检测细胞因子谱。在足月胎盘中观察到了SP-A、SP-D和MBL的转录本。与“NLc”组相比,“SLv”组的SP-D转录本和蛋白显著上调(p = 0.001),而SP-A转录本和蛋白则下调(p = 0.005)。胎盘和蜕膜组织中43 kDa和50 kDa的SP-D形式显著增加与自然分娩相关(p<0.05)。此外,“SLv”组胎盘的MMP-9切割形式的SP-D(25 kDa)显著高于“NLc”组(p = 0.002)。在nSP-D和rhSP-D处理的胎盘外植体中,与分娩相关的细胞因子IL-1α、IL-1β、IL-6、IL-8、IL-10、TNF-α和MCP-1呈剂量依赖性显著增加(p<0.05)。总之,该研究强调SP-A和SP-D蛋白与自然分娩相关,并且SP-D可能促成了母胎组织的促炎免疫环境。

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