Publications
243 results found
Kim SH, MacIntyre DA, Da Silva MF, et al., 2015, Oxytocin activates NF-kappa B-mediated inflammatory pathways in human gestational tissues, Molecular and Cellular Endocrinology, Vol: 403, Pages: 64-77, ISSN: 0303-7207
Human labour, both at term and preterm, is preceded by NF-κB-mediated inflammatory activation within the uterus, leading to myometrial activation, fetal membrane remodelling and cervical ripening. The stimuli triggering inflammatory activation in normal human parturition are not fully understood. We show that the neurohypophyseal peptide, oxytocin (OT), activates NF-κB and stimulates downstream inflammatory pathways in human gestational tissues. OT stimulation (1 pM–100 nM) specifically via its receptor (OTR) in human myometrial and amnion primary cells led to MAPK and NF-κB activation within 15 min and maximal p65-subunit nuclear translocation within 30 min. Both in human myometrium and amnion, OT-induced activation of the canonical NF-κB pathway upregulated key inflammatory labour-associated genes including IL-8, CCL5, IL-6 and COX-2. IKKβ inhibition (TPCA1; 10 µM) suppressed OT-induced NF-κB-p65 phosphorylation, whereas p65-siRNA knockdown reduced basal and OT-induced COX-2 levels in myometrium and amnion. In both gestational tissues, MEK1/2 (U0126; 10 µM) or p38 inhibition (SB203580; 10 µM) suppressed OT-induced COX-2 expression, but OT-induced p65-phosphorylation was only inhibited in amnion, suggesting OT activation of NF-κB in amnion is MAPK-dependent. Our data provide new insight into the OT/OTR system in human parturition and suggest that its therapeutic modulation could be a strategy for regulating both contractile and inflammatory pathways in the clinical context of term/preterm labour.
Georgakopoulou N, MacIntyre DA, Jimenez B, et al., 2015, <SUP>1</SUP>H-NMR-Based Characterisation of Maternal Plasma Metabolome During the Early 2nd Trimester Pregnancy Window, Publisher: SAGE PUBLICATIONS INC, Pages: 177A-178A, ISSN: 1933-7191
Kindinger L, MacIntyre D, Teoh TG, et al., 2015, Cervical Volume: A Longitudinal Observational Study in Pregnancy, Publisher: SAGE PUBLICATIONS INC, Pages: 153A-153A, ISSN: 1933-7191
Kindinger LM, MacIntyre DA, Teoh TG, et al., 2015, Prediction of Preterm Birth in Pre-Pregnancy Excisional Cervical Treatment, Publisher: SAGE PUBLICATIONS INC, Pages: 152A-152A, ISSN: 1933-7191
Sykes L, Rasheed ZBM, Lee YS, et al., 2015, 15-deoxy-D<SUP>12,14</SUP>Prostaglandin J2 Inhibits IL-1β Induced Contraction Associated Protein and Pro-Inflammatory Cytokine Expression in Human Cultured Amniocytes and Myocytes, Publisher: SAGE PUBLICATIONS INC, Pages: 243A-243A, ISSN: 1933-7191
Brown RG, Lee YS, Marchesi JR, et al., 2015, Erythromycin Treatment for PPROM Is Associated With a Reduction in Lactobacilli spp. and Increased Bacterial Diversity Within the Vaginal Microbiome, Publisher: SAGE PUBLICATIONS INC, Pages: 236A-236A, ISSN: 1933-7191
Migale R, MacIntyre DA, Lee YS, et al., 2015, Mouse Myometrial Transcriptome Analysis By RNAseq Shows Inflammation Is a Side-Effect, Not a Requisite, for Labor, Publisher: SAGE PUBLICATIONS INC, Pages: 66A-66A, ISSN: 1933-7191
Cook JR, MacIntyre DA, Samara E, et al., 2015, Oxytocin Modulates a Unique Set of Human Myometrial MicroRNAs, Publisher: SAGE PUBLICATIONS INC, Pages: 67A-67A, ISSN: 1933-7191
Brown RG, MacIntyre DA, 2014, Systematic review: Calcium channel blockers are effective as first line for tocolysis in the management of preterm labour, Evidence-Based Medicine, Vol: 19, ISSN: 1356-5524
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Brown RG, MacIntyre DA, 2014, Calcium channel blockers are effective as first line for tocolysis in the management of preterm labour., Evid Based Med, Vol: 19
Bray R, Jimenez B, MacIntyre D, et al., 2014, 1H-NMR BASED URINE METABONOMICS AS A NOVEL APPROACH TO OVERACTIVE BLADDER SYNDROME, 44th Annual Meeting of the International-Continence-Society (ICS), Publisher: WILEY-BLACKWELL, Pages: 923-924, ISSN: 0733-2467
Bray R, Jimenez B, MacIntyre D, et al., 2014, IS METABOLOMIC PROFILING USEFUL IN THE ASSESMENT OF WOMEN WITH LOWER URINARY TRACT SYMPTOMS?, 44th Annual Meeting of the International-Continence-Society (ICS), Publisher: WILEY-BLACKWELL, Pages: 926-927, ISSN: 0733-2467
Bray R, Jimenez B, MacIntyre D, et al., 2014, HIPPURIC ACID: A BIOMARKER FOR BLADDER PAIN SYNDROME, 44th Annual Meeting of the International-Continence-Society (ICS), Publisher: WILEY-BLACKWELL, Pages: 796-797, ISSN: 0733-2467
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- Citations: 1
Bray R, Jimenez B, MacIntyre DA, et al., 2014, 1H-NUCLEAR MAGNETIC RESONANCE URINARY METABOLOMICS IN OVERACTIVE BLADDER: DO NOCTURIA AND URGENCY HAVE SIMILAR METABOLIC PROFILES?, Publisher: SPRINGER LONDON LTD, Pages: S94-S95, ISSN: 0937-3462
Sykes L, MacIntyre DA, Teoh TG, et al., 2014, Anti-inflammatory prostaglandins for the prevention of preterm labour., Reproduction
Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. Tocolytics may therefore cause more harm by keeping the fetus in a hostile environment. Since inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has shifted towards exploring the potential for anti-inflammatory strategies. NF-κB is a transcription factor that controls the expression of many labour associated genes including COX-2, prostaglandins and the oxytocin receptor as well as key inflammatory genes. Targeting the inhibition of NF-κB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. Whilst prostaglandins are considered to be pro-labour and pro-inflammatory, the cyclopentenone prostaglandin 15-deoxy-Δ12,14PGJ2 (15dPGJ2) exhibits anti-inflammatory properties via the inhibition of NF-κB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15dPGJ2 also delays inflammation induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory prostaglandins may hold promise for the prevention of preterm labour and improved neonatal outcome.
Migale R, MacIntyre DA, Lee YS, et al., 2014, TLR4-mediated activation of AP-1 drives the expression of labour associated genes in mouse myometrium, Publisher: WILEY-BLACKWELL, Pages: E10-E10, ISSN: 1470-0328
Chandiramani M, Lee Y, Kindinger L, et al., 2014, 8.6 The evolution of the vaginal microbiome throughout uncomplicated pregnancy in a UK population., Pages: A12-A13
The vaginal microbiome plays an important role in maintaining reproductive health throughout pregnancy. Despite the presence of an 'abnormal' vaginal microbial community being associated with an increased risk of preterm birth, interventional trials of antibiotics have failed to demonstrate significant benefit, which is likely due to a poor understanding of the vaginal microbiome in pregnancy. We sought to characterise the vaginal microbiome in uncomplicated pregnancies in a UK-based cohort.
Cook JR, MacIntyre DA, Samara E, et al., 2014, hsa-miR-223 is differentially expressed in labouring and non-labouring human myometrium at term, Publisher: WILEY-BLACKWELL, Pages: E4-E4, ISSN: 1470-0328
Chandiramani M, Bennett PR, Brown R, et al., 2014, Vaginal Microbiome-Pregnant Host Interactions Determine a Significant Proportion of Preterm Labour, Fetal and Maternal Medicine Review
MacIntyre DA, Lee YS, Migale R, et al., 2014, Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice, FASEB JOURNAL, Vol: 28, Pages: 2358-2368, ISSN: 0892-6638
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- Citations: 82
Rosell M, Kaforou M, Frontini A, et al., 2014, Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 306, Pages: E945-E964, ISSN: 0193-1849
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- Citations: 267
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
MacIntyre DA, Lee YS, Marchesi J, et al., 2014, Preterm Premature Rupture of Membranes (PPROM) Is Associated with Disparate Vaginal Microbiomes That Are Correlated with Specific Urinary Metabolic Profiles, 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 246A-246A, ISSN: 1933-7191
Lee Y, Mitchell M, MacIntyre D, et al., 2014, Human Uterine Myometrial Cells Retain Key Functional Properties throughtout Culture and Passage, 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 243A-243A, 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
Chandiramani M, Bennett PR, Brown R, et al., 2014, Vaginal microbiome-pregnant host interactions determine a significant proportion of preterm labour, Fetal and Maternal Medicine Review, Vol: 25, Pages: 73-78, ISSN: 0965-5395
Preterm birth (PTB) has a global prevalence of 11.1% accounting for almost 15 million babies born each year before 37 weeks of gestation. It is a risk factor in over 50% of all neonatal deaths, which amounts to 1.1 million deaths annually. Preterm birth, especially at early gestational ages is associated with a high risk of long-term morbidity in survivors. Despite much research effort, PTB rates continue to rise, placing immense financial and emotional burden on society. In the US, the annual societal economic cost associated with PTB is $26.2 billion with an average of $51,600 being spent per infant born preterm. Preterm labour (PTL) accounts for 70% of these births, of which 25% are preceded by preterm pre-labour rupture of membranes (PPROM).
Migale R, MacIntyre DA, Lee YS, et al., 2013, TLR4-mediated activation of AP-1 drives the expression of labour associated genes in the mouse myometrium, RCOG Annual Academic Meeting 2013
Cook JR, MacIntyre DA, Samara E, et al., 2013, has-miR-223 is differentially expressed in labouring and non-labouring human myometrium at term, RCOG Annual Academic Meeting 2013
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
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