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Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)\/AP1- or NF-\u03baB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK\/AP-1 and NF-\u03baB, showed that selective inhibition of NF-\u03baB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK\/AP-1 but not NF-\u03baB, inhibition of JNK\/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK\/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection\/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain.<\/jats:p>","DOI":"10.1530\/rep-15-0258","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T22:20:02Z","timestamp":1437085202000},"page":"269-277","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":16,"title":["Specific inhibition of c-Jun N-terminal kinase delays preterm labour and reduces mortality"],"prefix":"10.1093","volume":"150","author":[{"given":"Grisha","family":"Pirianov","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Gene Transfer Technology Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Proteostasis Therapeutics 200 Technology Square Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Department of Biomedical and Forensic Sciences Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"MacIntyre","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Gene Transfer Technology Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Proteostasis Therapeutics 200 Technology Square Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Department of Biomedical and 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Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon N","family":"Waddington","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Institute for Women's Health, University College London, 86\u201396 Chenies Mews, London WC1E 6HX, UK 3 Suite 402, Cambridge, Massachusetts 02139, USA 4 Anglia Ruskin University, East Road, Cambridge CB1 1PT, UK"},{"name":"Gene Transfer Technology Group Department of Reproductive Biology, Institute of Reproductive and Developmental Biology, Imperial College London, 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