Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102853
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Type: Journal article
Title: Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth
Author: Chin, P.
Dorian, C.
Hutchinson, M.
Olson, D.
Rice, K.
Moldenhauer, L.
Robertson, S.
Citation: Scientific Reports, 2016; 6(1):36112-1-36112-13
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Peck Yin Chin, Camilla L. Dorian, Mark R. Hutchinson, David M. Olson, Kenner C. Rice, Lachlan M. Moldenhauer and Sarah A. Robertson
Abstract: Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (-)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed E. coli. Local induction by E. coli of inflammatory cytokine genes Il1b, Il6, Tnf and Il10 in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.
Keywords: Animals; Mice; Premature Birth; Inflammation; Naloxone; Lipopolysaccharides; Cytokines; Pregnancy; Female; Toll-Like Receptor 4
Description: Published: 07 November 2016
Rights: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030057918
DOI: 10.1038/srep36112
Grant ID: http://purl.org/au-research/grants/nhmrc/1026178
http://purl.org/au-research/grants/nhmrc/465423
http://purl.org/au-research/grants/arc/DP110100297
Appears in Collections:IPAS publications

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