{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:57:48Z","timestamp":1791478668930,"version":"4.3.4"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,17]],"date-time":"2014-03-17T00:00:00Z","timestamp":1395014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2014,5]]},"abstract":"Problem<\/jats:title>Toll\u2010like receptors (TLR<\/jats:styled-content>s) 2 and 5 induce inflammation via the adapter proteins myeloid differentiation factor 88 (M<\/jats:styled-content>yD<\/jats:styled-content>88) and TNFR<\/jats:styled-content>\u2010associated factor 6 (TRAF<\/jats:styled-content>6) and the transcription factor nuclear factor\u2010kappa B<\/jats:styled-content> (NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content>). The aims of this study were to determine the effects of the TLR<\/jats:styled-content>5 ligand flagellin and the TLR<\/jats:styled-content>2 ligand FSL<\/jats:styled-content>\u20101 on pro\u2010inflammatory and pro\u2010labour mediators in human fetal membranes and myometrium, and to establish whether their actions are dependent on M<\/jats:styled-content>yD<\/jats:styled-content>88, TRAF<\/jats:styled-content>6 and NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content>.<\/jats:p><\/jats:sec>Method of Study<\/jats:title>Tissue explants were performed to determine the effect of flagellin and FSL<\/jats:styled-content>\u20101 on pro\u2010labour mediators in fetal membranes and myometrium. siRNA<\/jats:styled-content> knockdown was performed in primary amnion and myometrium cells to determine the role of M<\/jats:styled-content>yD<\/jats:styled-content>88, TRAF<\/jats:styled-content>6 and NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>Flagellin and FSL<\/jats:styled-content>\u20101 increased pro\u2010inflammatory cytokines (IL<\/jats:styled-content>\u20106 and IL<\/jats:styled-content>\u20108), MMP<\/jats:styled-content>\u20109 expression and activity, and COX<\/jats:styled-content>\u20102 expression and prostaglandin release. siRNA<\/jats:styled-content> knockdown of TLR<\/jats:styled-content>2 decreased FSL<\/jats:styled-content>\u20101 induced production of IL<\/jats:styled-content>\u20106, IL<\/jats:styled-content>\u20108, COX<\/jats:styled-content>\u20102, prostaglandins and MMP<\/jats:styled-content>\u20109; similarly, siRNA<\/jats:styled-content> knockdown of TLR<\/jats:styled-content>5 decreased flagellin induced production of these pro\u2010labour mediators. The effects of flagellin and FSL<\/jats:styled-content>\u20101 are mediated by M<\/jats:styled-content>yD<\/jats:styled-content>88 and TRAF<\/jats:styled-content>6, as siRNA<\/jats:styled-content> knockdown of M<\/jats:styled-content>yD<\/jats:styled-content>88 and TRAF<\/jats:styled-content>6 decreased flagellin and FSL<\/jats:styled-content>\u20101 induced pro\u2010labour mediators. Additionally, the effects of flagellin and FSL<\/jats:styled-content>\u20101 are mediated via NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content>, as flagellin and FSL<\/jats:styled-content>\u20101 increased NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content> transcriptional activity, and the NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content> inhibitor BAY<\/jats:styled-content> 11\u20107082 attenuated flagellin and FSL<\/jats:styled-content>\u20101 induced expression and secretion of pro\u2010labour mediators.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>TLR<\/jats:styled-content>2 engagement by the synthetic lipoprotein FSL<\/jats:styled-content>\u20101 and TLR<\/jats:styled-content>5 engagement by bacterial flagellin enhances pro\u2010inflammatory and pro\u2010labour mediators in human fetal membranes and myometrium via M<\/jats:styled-content>yD<\/jats:styled-content>88\/TRAF<\/jats:styled-content>6\/NF<\/jats:styled-content>\u2010\u03baB<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12229","type":"journal-article","created":{"date-parts":[[2014,3,17]],"date-time":"2014-03-17T07:41:10Z","timestamp":1395042070000},"page":"401-417","source":"Crossref","is-referenced-by-count":59,"title":["The TLR<\/scp>2 Ligand FSL<\/scp>\u20101 and the TLR<\/scp>5 Ligand Flagellin Mediate Pro\u2010Inflammatory and Pro\u2010Labour Response via MyD88\/TRAF<\/scp>6\/NF<\/scp>\u2010\u03baB\u2010Dependent Signalling"],"prefix":"10.1111","volume":"71","author":[{"given":"Ratana","family":"Lim","sequence":"first","affiliation":[{"name":"Obstetrics Nutrition and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Heidelberg Vic. 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