Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong university, Shanghai, People's Republic of China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, People's Republic of China.
Inflamm Res. 2023 Apr;72(4):797-812. doi: 10.1007/s00011-023-01713-3. Epub 2023 Mar 6.
Sterile inflammation of fetal membranes is an indispensable event of normal parturition. However, triggers of sterile inflammation are not fully resolved. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver. Fetal membranes can also synthesize SAA1 but its functions are not well defined. Given the role of SAA1 in the acute phase response to inflammation, we postulated that SAA1 synthesized in the fetal membranes may be a trigger of local inflammation at parturition.
The changes of SAA1 abundance in parturition were studied in the amnion of human fetal membranes. The role of SAA1 in chemokine expression and leukocyte chemotaxis was examined in cultured human amnion tissue explants as well as primary human amnion fibroblasts. The effects of SAA1 on monocytes, macrophages and dendritic cells were investigated in cells derived from a human leukemia monocytic cell line (THP-1).
SAA1 synthesis increased significantly in human amnion at parturition. SAA1 evoked multiple chemotaxis pathways in human amnion fibroblasts along with upregulation of a series of chemokines via both toll-like receptor 4 (TLR4) and formyl peptide receptor 2 (FPR2). Moreover, SAA1-conditioned medium of cultured amnion fibroblasts was capable of chemoattracting virtually all types of mononuclear leukocytes, particularly monocytes and dendritic cells, which reconciled with the chemotactic activity of conditioned medium of cultured amnion tissue explants collected from spontaneous labor. Furthermore, SAA1 could induce the expression of genes associated with inflammation and extracellular matrix remodeling in monocytes, macrophages and dendritic cells derived from THP-1.
SAA1 is a trigger of sterile inflammation of the fetal membranes at parturition.
胎儿膜的无菌性炎症是正常分娩的一个不可或缺的事件。然而，无菌性炎症的触发因素尚未完全解决。血清淀粉样蛋白 A1（SAA1）是一种主要由肝脏产生的急性期蛋白。胎儿膜也可以合成 SAA1，但它的功能尚未明确。鉴于 SAA1 在炎症的急性期反应中的作用，我们推测在分娩时，胎儿膜中合成的 SAA1 可能是局部炎症的触发因素。
研究了人胎膜分娩时 SAA1 丰度的变化。在培养的人羊膜组织外植体以及原代人羊膜成纤维细胞中，研究了 SAA1 在趋化因子表达和白细胞趋化中的作用。在源自人类白血病单核细胞系（THP-1）的细胞中，研究了 SAA1 对单核细胞、巨噬细胞和树突状细胞的作用。
SAA1 的合成在人胎膜分娩时显著增加。SAA1 通过 Toll 样受体 4（TLR4）和甲酰肽受体 2（FPR2），在人羊膜成纤维细胞中引发多种趋化途径，同时上调一系列趋化因子。此外，培养的羊膜成纤维细胞条件培养基能够吸引几乎所有类型的单核白细胞，特别是单核细胞和树突状细胞，这与自发分娩时收集的培养羊膜组织外植体条件培养基的趋化活性一致。此外，SAA1 可以诱导源自 THP-1 的单核细胞、巨噬细胞和树突状细胞中与炎症和细胞外基质重塑相关的基因表达。
SAA1 是人胎膜分娩时无菌性炎症的触发因素。
