TRADD, TRAF2, RIP1 and TAK1 are required for TNF-α-induced pro-labour mediators in human primary myometrial cells.
TNF-α plays a central role in the processes of human labour and delivery. This study sought to determine the role of the adaptor proteins TNFR1-associated death domain protein (TRADD), TNF receptor-associated factor 2 (TRAF2), receptor interacting protein 1 (RIP1) and transforming growth factor beta-activated kinase 1 (TAK1) in TNF-α-induced formation of pro-labour mediators.



Human primary myometrial cells were transfected with siRNA against TRADD (siTRADD), TRAF2 (siTRAF2), RIP1 (siRIP1) or TAK1 (siTAK1), treated with TNF-α, and assayed for pro-inflammatory mediators expression.



siTRADD, siTRAF2, siRIP1 and siTAK1 significantly decreased TNF-α-induced IL-1α, IL-1β, IL-6, IL-8, MCP-1 mRNA expression and release of IL-6, IL-8 and MCP-1; and cyclooxygenase (COX)-2 expression and release of prostaglandin PGF2α. There was a significant attenuation of TNF-α-induced expression of adhesion molecules ICAM-1 and VCAM-1 mRNA with siTRADD, siTRAF2 or siRIP1. siTRADD and siRIP1 significantly attenuated TNF-α-induced MMP-9 mRNA expression and release and nuclear factor κB (NF-κB) transcriptional activity. There was a significant increase in TNF-α-induced sVCAM-1 release, MMP-9 mRNA expression and NF-κB activity with siTAK1.



TRADD, TRAF2, RIP1 and TAK1 are involved in TNF-α signalling in human myometrium. Further studies are required to determine whether inhibition of these proteins can prevent preterm birth.
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Ratana
R
Lim
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Gillian
G
Barker
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Martha
0000-0002-4744-6929
M
Lappas
D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015237:Dinoprost / Q000235:genetics; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007743:Labor, Obstetric; D020930:MAP Kinase Kinase Kinases / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009215:Myometrium / Q000166:cytology*; D016328:NF-kappa B / Q000235:genetics; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics*; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics*; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D051546:Cyclooxygenase 2; D016207:Cytokines; D015237:Dinoprost; D018799:Intercellular Adhesion Molecule-1; D020930:MAP Kinase Kinase Kinases; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D034741:RNA, Small Interfering; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053199:TNF Receptor-Associated Death Domain Protein; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000099151:MAP Kinase Kinase Kinase 7; C573420:ICAM1 protein, human; C496540:PTGS2 protein, human; C579270:MMP9 protein, human
TNF; inflammation; myometrium; pregnancy