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An inflammatory role of relaxin at the maternal-fetal interface

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Item Summary

Title: An inflammatory role of relaxin at the maternal-fetal interface
Authors: Horton, Jaime Saya
Keywords: maternal-fetal interface
inflammatory role
Issue Date: Dec 2010
Publisher: [Honolulu] : [University of Hawaii at Manoa], [December 2010]
Abstract: The human fetal membranes form the fetal container or gestational sac. This tissue with the maternal decidua forms a large, immunologically-unique interface crucial for maternal-fetal communication. Autocrine/paracrine signaling across this junction regulates successful embryo implantation, fetal growth and development, and contributes to the initiation of parturition. However, dysregulation of these signaling components contribute to pregnancy pathologies, often leading to fetal demise and/or preterm birth (PTB). PTB is a serious clinical problem, with evidence supporting the pathological activation of complex inflammatory mechanisms. Relaxin (RLN) is a peptide hormone produced by the corpus luteum and the choriodecidua. In this study, we have investigated the immunomodulatory effects of RLN on isolated decidual macrophages (DM), fibroblasts (DF), stromal cells (DSC) and chorionic cytotrophoblast (CyT), and characterized some of its mechanisms of action at term. In DM, low RLN levels (10, 100 nM) significantly (P<0.05) decreased secretion of GM-CSF and IL-8 in 4 h, shown to be due to its interaction with the glucocorticoid receptor (GR). However, longer treatment (24 h) caused significantly (P<0.01) increased IL-6 as a result of interaction with the RLN receptor, RXFP1, and increased cAMP. Although there were no effects of RLN on DF or DSC, RLN (100, 200 nM) treatment of CyT for 4 h significantly (P<0.05, P<0.01) increased IL-6, which was shown to be dependent on gene transcription and increased cAMP. In the presence of inflammation or infection, modeled by IL-1β or lipopolysaccharide (LPS) respectively, RLN significantly (P<0.05) augmented the GM-CSF, IL-6 and IL-8 responses by both CyT and DF. This response in CyT was shown to be independent of RLN interaction with either TLR4 or GR, suggesting preferential RLN-RXFP1 binding in these cells. Taken together, these results suggest that low levels of RLN present in normal pregnancy target the DM to cause immunosuppression, supporting pregnancy maintenance. However, either higher levels or more chronic exposure to RLN would target the DM, CyT and DF to cause immunostimulation, and in addition, would augment any inflammatory response already present. Such a florid cytokine response would trigger the pathways for the terminal events leading to preterm labor and delivery.
Description: Ph.D. University of Hawaii at Manoa 2010.
Includes bibliographical references.
Appears in Collections:Ph.D. - Cell and Molecular Biology

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