Amnion-derived serum amyloid A1 participates in sterile inflammation of fetal membranes at parturition

ABSTRACT: Sterile inflammation of the fetal membranes is an indispensable event of normal parturition. However, triggers of the sterile inflammation are not fully resolved. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver, which is believed to be implicated in the host inflammatory response to ensure early survival. Emerging evidence indicates that SAA1 can also be synthesized in extra-hepatic tissues including gestational tissues. Moreover, SAA1 synthesis is greatly enhanced in gestational tissues at parturition. Given the inflammatory actions of SAA1, we hypothesized that increased SAA1 synthesis locally in the fetal membranes may act as a humoral trigger of sterile inflammation of the fetal membranes at parturition. Here, by using transcriptomic sequencing and multiplex immunoassay, we found that multiple pathways related to chemotaxis were evoked by SAA1 in human amnion fibroblasts along with upregulation of a series of chemokines, particularly CCL3, CXCL6 and CCL20. Mechanistic studies showed that both toll-like receptor 4 (TLR4) and formyl peptide receptor 2 (FPR2) was involved in the induction of chemokines by SAA1. Moreover, SAA1-conditioned culture medium of amnion fibroblasts was capable of chemoattracting virtually all types of mononuclear leukocytes, particularly monocytes and dendritic cells, which reconciled well with the chemotactic activity of conditioned culture medium of amnion tissue explants collected from spontaneous labor. The infiltration of monocytes and dendritic cells to the fetal membranes at parturition was confirmed both morphologically with immunohistochemical staining and quantitatively with Western blotting. Additionally, SAA1 could also activate monocytes/macrophages and dendritic cells towards a proinflammatory phenotype. Conclusively, increased local SAA1 synthesis may trigger sterile inflammation of the fetal membranes at parturition by stimulating chemokine production initially in local cells resulting in increased chemotaxis of mononuclear leukocytes to the membranes to facilitate their transition towards the proinflammatory phenotype.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217734 | GEO | 2025/11/10

REPOSITORIES: GEO