| Relaxin augments the inflammatory IL6 response in the choriodecidua. | |
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MedLine Citation:
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PMID: 22386961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intrauterine infection frequently leads to preterm birth (PTB), with the pathophysiology involving activation of the innate immune system and its associated inflammatory response. The choriodecidua produces relaxin (RLN) and elevated levels are associated with preterm premature rupture of the fetal membranes. However, it is not increased in bacterially-mediated PTB, but may act as an endogenous sterile inflammatory mediator. Elevated systemic RLN levels from the corpus luteum are also associated with PTB, but the mechanism is unknown. In clinical obstetrics, intrauterine inflammation or infection can coexist with elevated RLN. Therefore, in this study, we further characterized the effects of RLN alone or together with an inflammatory mediator on the production of IL1B, CSF2 (GM-CSF), IL6, IL8 and TNF, from chorionic cytotrophoblasts (CyT), decidual fibroblasts (DF) and stromal cells (DSC), using interleukin-1 beta (IL1B) to mimic sterile inflammation or lipopolysaccharide (LPS) for bacterial infection. Endogenous differences between the cells showed that the CyT expressed more RLN, its receptor RXFP1 and the RXFP1 splice variant D. CyT also showed the most robust cAMP response to RLN with increased IL6 secreted after 4 h, preceded by increased transcription at 1 h, likely due to activation of RXFP1 and cAMP. When all cell types were treated with IL1B and RLN, RLN augmented secretion of IL6 and IL8 from CyT and DF, but not DSC. Similarly, RLN augmented LPS-induced IL6 secretion from CyT and DF. Despite the structural similarity between TLR4 and RXFP1, blocking TLR4 in CyT had no effect on RLN-induced IL6 secretion, suggesting specific activation of RXFP1. Thus, we have shown that in the presence of a low level of intrauterine inflammation/infection, elevated RLN could act on the CyT and DF to augment the inflammatory response, contributing to the pathophysiology of PTB. SUMMARY: RLN augments the inflammatory responses induced by IL1B or LPS in chorionic cytotrophoblasts and decidual fibroblasts. |
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Authors:
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J S Horton; S Y Yamamoto; G D Bryant-Greenwood |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-03-03 |
Journal Detail:
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Title: Placenta Volume: 33 ISSN: 1532-3102 ISO Abbreviation: Placenta Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-02 Completed Date: 2012-08-03 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 8006349 Medline TA: Placenta Country: England |
Other Details:
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Languages: eng Pagination: 399-407 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Cell and Molecular Biology, University of Hawaii, John A. Burns School of Medicine, 651 Ilalo Street, Bioscience Building, Honolulu, HI 96813, USA. jshorton@hawaii.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cyclic AMP
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metabolism Extraembryonic Membranes / metabolism* Female Humans Interleukin-1beta / metabolism Interleukin-6 / metabolism*, secretion Receptors, G-Protein-Coupled / metabolism Receptors, Peptide / metabolism Relaxin / metabolism* Toll-Like Receptor 4 / metabolism Trophoblasts / metabolism*, secretion |
| Grant Support | |
ID/Acronym/Agency:
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HD24314/HD/NICHD NIH HHS; R01 HD024314-10/HD/NICHD NIH HHS; U54 RR014607-10/RR/NCRR NIH HHS; U54 RR014607-10/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/IL1B protein, human; 0/IL6 protein, human; 0/Interleukin-1beta; 0/Interleukin-6; 0/RXFP1 protein, human; 0/Receptors, G-Protein-Coupled; 0/Receptors, Peptide; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 60-92-4/Cyclic AMP; 9002-69-1/Relaxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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