SLIT 3 is Increased in Supracervical Human Foetal Membranes and in Labouring Myometrium and Regulates Pro‐Inflammatory Mediators

Problem Inflammation is associated with preterm birth, a worldwide healthcare issue. SLIT 3 has a role in inflammation, and thus, the purpose of this study was to determine the effect of SLIT 3 on labour mediators in human gestational tissues. Method of study SLIT 3 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 ). SLIT 3 gene silencing was achieved using si RNA in primary amnion and myometrial cells. Pro‐inflammatory and pro‐labour mediators were evaluated by q RT ‐ PCR , ELISA and gelatin zymography. Results SLIT 3 expression was greater in foetal membranes from the SCS compared with DS and in myometrium after term spontaneous labour onset. SLIT 3 si RNA 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, SLIT 3 si RNA knockdown decreased IL ‐1β‐induced COX ‐2 expression and prostaglandin PGE 2 release. There was no effect of SLIT 3 si RNA on IL ‐1β‐induced NF ‐κ B transcriptional activity. Conclusion Our results demonstrate that SLIT 3 is increased with labour, and both our amnion and our myometrial studies describe a pro‐inflammatory effect of SLIT 3 in these tissues.