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The majority of cases of early preterm labour are associated with infection\/inflammation, which places the fetal central nervous system at risk. Targeting immune activation is therefore an appealing therapeutic strategy for the prevention of preterm labour and neonatal brain injury. The expression of many labour\u2010associated and inflammatory\u2010response genes is controlled by the transcription factors nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B) and activator protein\u20101 (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101), which makes them therapeutic targets of interest. Sulfasalazine (<jats:styled-content style=\"fixed-case\">SASP<\/jats:styled-content>) has been shown to inhibit <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B and reduce lipopolysaccharide\u2010induced cytokine concentrations in fetal membrane explants and reduce the rate of <jats:italic>Escherichia coli<\/jats:italic>\u2010induced preterm labour in mice. Its effects upon <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 in the context of pregnancy are unknown. In this study the effect of <jats:styled-content style=\"fixed-case\">SASP<\/jats:styled-content> on interleukin\u20101<jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>) \u2010induced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B and <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 activity, cytokine production and cyclo\u2010oxygenase\u20102 (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102) expression was examined in amniocytes and myocytes. A supra\u2010therapeutic concentration (5\u00a0m<jats:sc>m<\/jats:sc>) was required to inhibit <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b70001) in amniocytes and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:italic>\u03ba<\/jats:italic>B (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b701), <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b701) and <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b705) in myocytes. Despite inhibiting <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced cytokines, a basal increase in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b701), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b70001) and tumour necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>) (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b7001) was seen with 5\u00a0m<jats:sc>m <\/jats:sc><jats:styled-content style=\"fixed-case\">SASP<\/jats:styled-content> in amniocytes, and significant cytotoxic effects were seen in myocytes. The therapeutic concentration of 0\u00b7015\u00a0m<jats:sc>m<\/jats:sc> had no inhibitory effects on pro\u2010inflammatory mediators, but led to an augmented response to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b701), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b705) and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b705) in amniocytes and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0\u00b705) in myocytes. <jats:styled-content style=\"fixed-case\">SASP<\/jats:styled-content> is therefore an unlikely therapeutic candidate for the prevention of inflammation\u2010induced preterm labour.<\/jats:p>","DOI":"10.1111\/imm.12534","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T08:11:52Z","timestamp":1442995912000},"page":"630-644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sulfasalazine augments a pro\u2010inflammatory response in interleukin\u20101<i>\u03b2<\/i>\u2010stimulated amniocytes and myocytes"],"prefix":"10.1111","volume":"146","author":[{"given":"Lynne","family":"Sykes","sequence":"first","affiliation":[{"name":"Department of Surgery and Cancer Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacie R.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahirrah B. 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