Stella Liong1,2, Martha Lappas1,2. 1. Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic., Australia. 2. Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Vic., Australia.
Abstract
PROBLEM: Sterile 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 STUDY: Localization 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. RESULTS: HO-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. CONCLUSION: Collectively, 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.
PROBLEM: Sterile 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 STUDY: Localization 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. RESULTS:HO-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. CONCLUSION: Collectively, 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.
Authors: Anna Wrona; Veronika Aleksandrovych; Tomasz Bereza; Paweł Basta; Anna Gil; Magdalena Ulatowska-Białas; Małgorzata Mazur-Laskowska; Kazimierz Pityński; Krzysztof Gil Journal: Int J Mol Sci Date: 2022-05-31 Impact factor: 6.208
Authors: Marie Francoise Mukanyangezi; Lucie Podmolíková; Wurood Al Hydad; Gunnar Tobin; Daniel Giglio Journal: PLoS One Date: 2019-04-18 Impact factor: 3.240
Authors: Zahirrah B M Rasheed; Yun S Lee; Sung H Kim; Ranjit K Rai; Camino S M Ruano; Eberechi Anucha; Mark H F Sullivan; David A MacIntyre; Phillip R Bennett; Lynne Sykes Journal: Front Immunol Date: 2020-08-25 Impact factor: 7.561