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The Stress‐responsive Heme Oxygenase ( HO )‐1 Isoenzyme is Increased in Labouring Myometrium where it Regulates Contraction‐associated Proteins
Author(s) -
Liong Stella,
Lappas Martha
Publication year - 2015
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12366
Subject(s) - heme oxygenase , myometrium , cytokine , inflammation , receptor , microbiology and biotechnology , chemistry , proinflammatory cytokine , gene expression , endocrinology , biology , medicine , heme , immunology , biochemistry , uterus , gene , enzyme
Problem Sterile inflammation through activation of cytokine receptor signalling pathways and viral or bacterial infection via activation of Toll‐like receptors ( TLR s) 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. si RNA 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 ( TLR 5 ligand), viral ds RNA analogue polyinosinic polycytidylic acid (poly(I:C)) ( TLR 3 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 si RNA 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.