Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Optineurin suppression activates the mediators involved in the terminal effector pathways of human labour and delivery

Ratana Lim A B , Gillian Barker A B and Martha Lappas A B C

A Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Vic. 3084, Australia.

B Mercy Perinatal Research Centre, Mercy Hospital for Women, 4th Floor, 163 Studley Rd, Heidelberg, Vic. 3084, Australia.

C Corresponding author. Email: mlappas@unimelb.edu.au

Reproduction, Fertility and Development - https://doi.org/10.1071/RD15494
Submitted: 25 November 2015  Accepted: 19 February 2016   Published online: 2 May 2016

Abstract

Spontaneous preterm birth remains the major cause of neonatal death and morbidity. Studies in non-gestational tissues report that optineurin (OPTN) is critical in the termination of NFKB1 activity and control of inflammation, central features of spontaneous preterm birth. The aims of the present study were to determine: (1) OPTN expression in fetal membranes and the myometrium during labour; (2) the effects of IL1B on OPTN expression in primary myometrial cells; and (3) the effects of OPTN short interference (si) RNA on IL1B-stimulated proinflammatory and prolabour mediators. OPTN mRNA and protein expression was significantly decreased with spontaneous term labour in fetal membranes and the myometrium. Although there was no effect of spontaneous preterm labour on OPTN expression in fetal membranes, there was decreased OPTN expression in membranes with chorioamnionitis and myometrial cells treated with 1ng mL–1 IL1B for 1 or 6 h. In cells transfected with OPTN siRNA, significant increases were seen in IL1B-stimulated IL6, tumour necrosis factor, CXCL8 and monocyte chemoattractant protein-1 mRNA expression and release, cyclo-oxygenase-2 and prostanoid PTGFR receptor mRNA expression and the release of prostaglandin F. There was no change in IL1B-stimulated NFKBIA expression; however, there was increased NFKB1 p65 DNA-binding activity. The results of the present study suggest that OPTN is a negative regulator of inflammation-induced prolabour mediators.

Additional keywords: infection, inflammation, myometrium, preterm birth.


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