• Stella Liong and Martha Lappas.
• Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic., Australia.
• Am. J. Reprod. Immunol. 2015 Jul 1; 74 (1): 62-76.

ProblemSterile inflammation through activation of cytokine receptor signalling pathways and viral or bacterial infection via activation of Toll-like receptors (TLRs) induces a cascade of events that leads to myometrial contractions and spontaneous preterm delivery. In non-pregnant tissues, heme oxygenase-1 (HO-1) is thought to play a central role in regulating the inflammatory response. Thus, the aims of this study were to determine the effect of human term labour on HO-1 expression in human myometrium and to investigate the role of HO-1 in myometrial primary cells in response to cytokine- and TLR ligand-induced inflammation.Method Of StudyLocalization and expression of HO-1 protein in human myometrial tissues were determined using IHC. Western blot analysis and qRT-PCR were also used to determine HO-1 protein and gene expression, respectively, in human myometrium. siRNA knock-down of HO-1 in myometrial primary cells was used to determine its role in response to inflammatory stimuli.ResultsHO-1 gene expression and protein expression were increased in term labouring myometrium compared with non-labouring myometrium. Bacterial flagellin (TLR5 ligand), viral dsRNA analogue polyinosinic polycytidylic acid (poly(I:C)) (TLR3 ligand) and pro-inflammatory cytokines IL-1β and TNF-α induced pro-inflammatory cytokine (IL-6 and IL-8) mRNA expression and release in myometrial cells. IL-1β also induced COX-2 mRNA expression and prostaglandin release. HO-1 siRNA knock-down significantly decreased the expression and secretion of these prolabour mediators. Additionally, flagellin, poly(I:C), IL-1β, and TNF-α-induced NF-κB transcriptional activity were suppressed in HO-1-deficient myometrial cells.ConclusionCollectively, these findings in myometrium indicate HO-1 expression is increased with labour and exerts pro-inflammatory effects via NF-κB during cytokine- and TLR ligand-induced inflammation.© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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