title: SLIT3 is increased in supracervical human foetal membranes and in labouring myometrium and regulates pro-inflammatory mediators.
abstract: OBJECTIVE
  Inflammation is associated with preterm birth, a worldwide healthcare issue. SLIT3 has a role in inflammation, and thus, the purpose of this study was to determine the effect of SLIT3 on labour mediators in human gestational tissues.
  
  
  METHODS
  SLIT3 protein expression was performed using immunohistochemistry in foetal membranes and myometrium with no labour and after labour. Foetal membranes were also obtained from a distal site (DS) and supracervical site (overlying the cervix; SCS). SLIT3 gene silencing was achieved using siRNA in primary amnion and myometrial cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography.
  
  
  RESULTS
  SLIT3 expression was greater in foetal membranes from the SCS compared with DS and in myometrium after term spontaneous labour onset. SLIT3 siRNA in primary amnion and myometrial cells decreased IL-1β-induced pro-inflammatory cytokine gene expression and release (IL-6 and IL-8) and MMP-9 gene expression and release. In amnion cells, SLIT3 siRNA knockdown decreased IL-1β-induced COX-2 expression and prostaglandin PGE2 release. There was no effect of SLIT3 siRNA on IL-1β-induced NF-κB transcriptional activity.
  
  
  CONCLUSIONS
  Our results demonstrate that SLIT3 is increased with labour, and both our amnion and our myometrial studies describe a pro-inflammatory effect of SLIT3 in these tissues.
authors.affiliation: Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic., Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Vic., Australia.
authors.forename: Ratana
authors.initials: R
authors.lastname: Lim
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000650:Amnion / Q000166:cytology; D002584:Cervix Uteri / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007745:Labor Onset / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000473:pathology; D047928:Premature Birth / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D014158:Transcription, Genetic
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; C498990:SLIT3 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
keywords: Foetal membranes; SLIT3; human labour; inflammation; myometrium