Publications
193 results found
Yulia A, Georgiou EX, Das A, et al., 2014, Enhancement of Anti-Inflammatory Effect by the Combination of Progesterone and cAMP on IL-1b-Stimulated Human Myometrial Cells., REPRODUCTIVE SCIENCES, Vol: 21, Pages: 111A-111A, ISSN: 1933-7191
Cook JR, MacIntyre DA, Samara E, et al., 2014, Identification of Differentially Expressed MicroRNAs in Labouring and Non-Labouring Human Myometrium at Term., 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 138A-138A, ISSN: 1933-7191
Ibeto L, Chandiramani M, Cook JR, et al., 2014, The Risk of Preterm Birth Associated with Uterine Anomalies and the Clinical Utility of Serial Measurement of Cervical Length, REPRODUCTIVE SCIENCES, Vol: 21, Pages: 253A-253A, ISSN: 1933-7191
Kim SH, Blanks A, Thornton S, et al., 2014, Oxytocin Receptor Antagonist, Atosiban, Drives Proinflammatory Effects in Human Amnion Via G<sub>ai</sub> Signaling., 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 111A-111A, ISSN: 1933-7191
Da Silva MAF, Kim SH, Bennett PR, et al., 2014, Oxytocin Activates NF-kB in Human Myometrium, 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 241A-241A, ISSN: 1933-7191
Nawathe A, Hye KS, Savvidou M, et al., 2014, Placental Expression of IGFs and Their Binding Proteins in Pregnancies Affected by Growth Disorders, Diabetes and Obesity., REPRODUCTIVE SCIENCES, Vol: 21, Pages: 294A-294A, ISSN: 1933-7191
Nawathe A, Hye KS, Savvidou M, et al., 2014, Effect of Adiponectin on IL-6 and COX-2 Expression in Term Placental Explants, REPRODUCTIVE SCIENCES, Vol: 21, Pages: 370A-370A, ISSN: 1933-7191
Cook JR, MacIntyre DA, Bennett P, et al., 2013, Specific microRNAs are differentially expressed in labouring and non-labouring human myometrium at term, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 120, Pages: 13-14, ISSN: 1470-0328
Kim SH, Blanks A, Thornton S, et al., 2013, Activation of NF-κB in Human Amnion Is Mediated through G<sub>ai</sub> and Is Mimicked by the Oxytocin Receptor Antagonist - Atosiban., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 122A-122A, ISSN: 1933-7191
MacIntyre DA, Migale R, Lee YS, et al., 2013, TLR4-Mediated Activation of AP1 Via JNK Induces Preterm Labour in the Mouse., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 296A-296A, ISSN: 1933-7191
Lee Y, Sooranna SR, Terzidou V, et al., 2012, Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes, JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol: 16, Pages: 2487-2503, ISSN: 1582-1838
The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF‐κB activation. The negative interaction between NF‐κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF‐κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter‐relationship, we have used small interfering (si) RNA‐mediated knock‐down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL‐1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR‐knock‐down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR‐induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro‐inflammatory gene networks induced by IL‐1β and that only MMP10 was significantly regulated in opposite directions by IL‐1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR.
Lim S, MacIntyre DA, Lee YS, et al., 2012, Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 45
Khanjani S, Terzidou V, Johnson MR, et al., 2012, NF kappa B and AP-1 Drive Human Myometrial IL8 Expression, MEDIATORS OF INFLAMMATION, Vol: 2012, ISSN: 0962-9351
The uterine expression of the chemokine IL8 increases dramatically with the onset of labour both at term and preterm. The IL8 promoter contains binding sites for the transcription factors nuclear factor-kappa B (NFκB), activator protein-1 (AP-1), and CCAAT/enhancer-binding protein (CEBP). In this study we investigated the roles of these transcription factors in IL1B regulation of the IL8 gene in human myometrium. Using chromatin immune precipitation (ChIP) assay, we showed that each of NFκB, CEBP, and AP-1 binds to the IL8 promoter upon IL1B stimulation. To examine the relative importance of each site in IL8 gene expression, site-directed mutagenesis of each of these sites was performed. We found that the NFκB site was essential for basal and IL1B-stimulated gene expression. Mutation of the AP-1 site reduced both basal and IL1B-stimulated expression but to a lesser extent. Mutation of the CEBP site had no effect upon basal expression but eliminated the IL1B response. Small interfering RNA (siRNA) silencing of NFκB abolished the IL8 response to IL1B significantly; siRNA against AP-1 reduced it to a lesser extent whilst knockdown of CEBP enhanced the response. Our data confirms a central and essential role for NFκB in regulation of IL8 in human myometrium.
Lee YS, MacIntyre DA, Pirianov G, et al., 2012, Inhibition of AP1 Delays LPS-Induced Preterm Labour and Improves Pup Outcome in the Murine Model, Publisher: SAGE PUBLICATIONS INC, Pages: 120A-120A, ISSN: 1933-7191
Webster SNE, Wales NM, Terzidou V, et al., 2012, Pregnancy Outcome Following History Indicated Abdominal Cerclage, REPRODUCTIVE SCIENCES, Vol: 19, Pages: 373A-374A, ISSN: 1933-7191
Kim SH, Blanks A, Thornton S, et al., 2012, Oxytocin Mediates COX-2 Expression Via NF-κB and MAPK Pathway., Publisher: SAGE PUBLICATIONS INC, Pages: 184A-184A, ISSN: 1933-7191
Read JE, Kim SH, Tchipeva D, et al., 2012, Bile Acids Upregulate the Oxytocin Receptor and Increase Contractility in Human Myometrium, Publisher: SAGE PUBLICATIONS INC, Pages: 198A-198A, ISSN: 1933-7191
Tchipeva D, Semertzidou A, Read J, et al., 2012, Suppression of the SUMO Pathway in Human Myometrium Modulates PR and NF-kB Signalling., Publisher: SAGE PUBLICATIONS INC, Pages: 187A-187A, ISSN: 1933-7191
Takahashi J, Kim SH, Sermertzidou A, et al., 2012, Regulation of Sumo-Pathway Enzymes upon Inflammatory Stress and Labour, 59th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation, Pages: 187A-187A
Khanjani S, Terzidou V, Lee YS, et al., 2011, Synergistic Regulation of Human Oxytocin Receptor Promoter by CCAAT/Enhancer-Binding Protein and RELA, BIOLOGY OF REPRODUCTION, Vol: 85, Pages: 1083-1088, ISSN: 0006-3363
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- Citations: 9
Kim SH, Blanks A, Thornton S, et al., 2011, Cytokines Regulated by Oxytocin in Human Amnion, Pages: 299A-299A, ISSN: 1933-7191
Semertzidou A, Brosens J, Bennett PR, et al., 2011, SUMO Modification Is Linked to the Process of Human Labor by Modulating PR Signalling, REPROD SCI, Vol: 18, Pages: 299A-300A, ISSN: 1933-7191
Kim SH, Blanks A, Thornton S, et al., 2011, Expression and Regulation of cPLA2 Isoforms in Human Amnion, Pages: 300A-300A, ISSN: 1933-7191
A Semertzidou, J Brosens, PR Bennett, et al., 2011, SUMO modification is linked to the process of human labor by modulating PR signalling, 58th Annual Scientific Meeting of SGI, Miami, USA
SH Kim, A Blanks, S Thornton, et al., 2011, Cytokines regulated by oxytocin in human amnion, 58th Annual Scientific Meeting of SGI, Miami, USA
SH Kim, A Blanks, S Thornton, et al., 2011, Expression and Regulation of cPLA2 Isoforms in Human Amnion, 58th Annual Scientific Meeting of SGI, Miami, USA
Terzidou V, Blanks AM, Kim SH, et al., 2011, Labor and Inflammation Increase the Expression of Oxytocin Receptor in Human Amnion, BIOL REPROD, Vol: 84, Pages: 546-552, ISSN: 0006-3363
Lee YS, Nelson S, Bollopragada S, et al., 2011, Transcriptomic Analysis of Human Myometrium Supports Inflammation but Not PR-Mediated Functional Progesterone Withdrawal as a Mechanism for Changes in Gene Expression with Labour, REPROD SCI, Vol: 18, Pages: 242A-242A, ISSN: 1933-7191
Khanjani S, Kandola MK, Lindstrom TM, et al., 2010, NF-kB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term, Journal of Cellular and Molecular Medicine, Vol: 15, Pages: 809-824, ISSN: 1582-4934
The onset of human labour resembles inflammation with increased synthesis of prostaglandins and cytokines. There is evidence from rodent models for an important role for nuclear factor-κB (NF-κB) activity in myometrium which both up-regulates contraction-associated proteins and antagonizes the relaxatory effects of progesterone. Here we show that in the human, although there are no differences in expression of NF-κB p65, or IκB-α between upper- or lower-segment myometrium or before or after labour, there is nuclear localization of serine-256-phospho-p65 and serine-536-phospho-p65 in both upper- and lower-segment myometrium both before and after the onset of labour at term. This shows that NF-κB is active in both upper and lower segment prior to the onset of labour at term. To identify the range of genes regulated by NF-κB we overexpressed p65 in myocytes in culture. This led to NF-κB activation identical to that seen following interleukin (IL)-1β stimulation, including phosphorylation and nuclear translocation of p65 and p50. cDNA microarray analysis showed that NF-κB increased expression of 38 genes principally related to immunity and inflammation. IL-1β stimulation also resulted in an increase in the expression of the same genes. Transfection with siRNA against p65 abolished the response to IL-1β proving a central role for NF-κB. We conclude that NF-κB is active in myocytes in both the upper and lower segment of the uterus prior to the onset of labour at term and principally regulates a group of immune/inflammation associated genes, demonstrating that myocytes can act as immune as well as contractile cells.
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