Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts.
Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts.
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人羊膜成纤维细胞中血清淀粉样蛋白 A1 诱导促炎基因
DOI：
10.1038/s41598-017-00782-9
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发表时间：
2017-04-06
影响因子：
4.6
通讯作者：
Sun K
中科院分区：
文献类型：
--
作者：
Li W;Wang W;Zuo R;Liu C;Shu Q;Ying H;Sun K
血清淀粉样蛋白A1（SAA 1）是一种急性反应蛋白，主要由肝脏在感染过程中产生。然而，它仍然是未知的SAA 1是否可以产生在人类胎膜中，它能够引发相关的事件，劳动开始。我们证明SAA 1在羊膜的成纤维细胞和上皮细胞以及绒毛膜的滋养层细胞中表达。在人羊膜成纤维细胞中的进一步研究表明，白细胞介素-1 β（IL-1β）和皮质醇单独或协同增加SAA 1的产生，并且SAA 1反过来诱导IL-1β、白细胞介素-6（IL-6）、环氧合酶-2（考克斯-2）的表达和PGE 2的产生。SAA 1的这些作用是通过Toll样受体4（TLR 4）激活NF-κB、p38和ERK 1/2途径介导的。TLR 4的抑制不仅减弱了SAA 1诱导的NF-κB、p38和ERK 1/2的活化，而且增加了IL-1β、IL-6和考克斯-2的表达。此外，SAA 1表达增加，在人羊膜组织自然分娩。总之，这项研究首次证明了SAA 1可以在人胎膜中产生，这可以在促炎细胞因子和糖皮质激素的存在下被极大地诱导，从而产生与分娩相关的作用。
Serum amyloid A1 (SAA1) is an acute response protein, which is mainly produced by the liver, during infection. However, it remains unknown whether SAA1 can be produced in human fetal membranes where it is able to elicit events pertinent to labor initiation. We demonstrated that SAA1 was expressed in the fibroblasts and epithelium of the amnion and the trophoblasts of the chorion. Further study in human amnion fibroblasts showed that SAA1 production was augmented by interleukin-1β (IL-1β) and cortisol alone and synergistically, and SAA1 in turn induced the expression of IL-1β, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and PGE2 production. These effects of SAA1 were mediated through activation of the NF-κB, p38 and ERK1/2 pathways via the toll-like receptor 4 (TLR4). Inhibition of TLR4 attenuated not only SAA1-induced activation of NF-κB, p38 and ERK1/2 but also increases in IL-1β, IL-6 and COX-2 expression. Moreover, SAA1 expression was increased in human amnion tissue following spontaneous labor. In conclusion, this study has demonstrated for the first time that SAA1 can be produced in human fetal membranes, which can be greatly induced in the presence of proinflammatory cytokines and glucocorticoids thereby producing effects associated with parturition.