Publications
282 results found
Campbell JP, Mackenzie MJ, Yentis SM, et al., 2012, An evaluation of the ability of leucocyte depletion filters to remove components of amniotic fluid*, ANAESTHESIA, Vol: 67, Pages: 1152-1157, ISSN: 0003-2409
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- Citations: 11
Chen L, Sooranna SR, Lei K, et al., 2012, Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells, Journal of Cellular and Molecular Medicine, Vol: 16, Pages: 1447-1460, ISSN: 1582-4934
Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contraction‐associated protein expression in myometrial cells and to promote oxytocin‐driven myometrial contractility. Cyclo‐oxygenase‐2 (COX‐2) is the rate‐limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX‐2 expression, synthesis and activity. Three cAMP agonists (8‐bromo‐cAMP, forskolin and rolipram) increased COX‐2 mRNA expression and further studies confirmed that this was associated with COX‐2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP‐effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP‐effector PDZ‐GEF1‐2, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX‐2 expression and that PGE2 acts through EP‐2 to activate MAPK and increase COX‐2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.
Lei K, Sooranna SR, Bennett PR, et al., 2012, MKP-1 and GR Mediate Progesterone-Induced COX-2 Repression in Human Myometrium., REPRODUCTIVE SCIENCES, Vol: 19, Pages: 185A-185A, ISSN: 1933-7191
Sooranna SR, Hua R, Xu H, et al., 2012, The Effect of Pregnancy on Cardiac Chemokine Gene Expression in Mice, REPRODUCTIVE SCIENCES, Vol: 19, Pages: 191A-191A, ISSN: 1933-7191
Herbert BR, Hua R, Waddington SN, et al., 2012, Absence of Maternal CCR2 Reduces the Adverse Effects of LPS-Induced Inflammation on Neonatal Outcome, REPRODUCTIVE SCIENCES, Vol: 19, Pages: 120A-120A, ISSN: 1933-7191
Lei K, Sooranna SR, Bennett PR, et al., 2012, Gene Networks and Cellular Functions That Are Regulated through Progesterone and Glucocorticoid Receptors in Human Myometrial Cells., REPRODUCTIVE SCIENCES, Vol: 19, Pages: 184A-185A, ISSN: 1933-7191
Malawana J, Howe L, Hua R, et al., 2012, Immunomodulation in Preterm Labour: An Answer to <i>In Utero</i> Neurological Insult., REPRODUCTIVE SCIENCES, Vol: 19, Pages: 185A-185A, ISSN: 1933-7191
Hua R, Pease JE, Sooranna SR, et al., 2012, Stretch and Inflammatory Cytokines Drive Myometrial Chemokine Expression Via NF-κB Activation, ENDOCRINOLOGY, Vol: 153, Pages: 481-491, ISSN: 0013-7227
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- Citations: 67
Alexander HA, Sooranna SR, Myatt L, et al., 2012, Myometrial Tumor Necrosis Factor-α Receptors Increase With Gestation and Labor and Modulate Gene Expression Through Mitogen-Activated Kinase and Nuclear Factor-κB, REPRODUCTIVE SCIENCES, Vol: 19, Pages: 43-54, ISSN: 1933-7191
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- Citations: 12
Lei K, Chen L, Cryar BJ, et al., 2011, Uterine Stretch and Progesterone Action, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 96, Pages: E1013-E1024, ISSN: 0021-972X
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- Citations: 29
Sooranna SR, Lei K, Bennett PR, et al., 2011, Mechanical Stretch of Cultured Human Uterine Myocytes Leads to Increased Expression of Metallothioneins and Heat Shock 70kDa Proteins, REPRODUCTIVE SCIENCES, Vol: 18, Pages: 299A-299A, ISSN: 1933-7191
Hua R, Lei K, Herbert B, et al., 2011, Uterine Chemokine Expression in Progesterone Delayed Labour in Mice, REPRODUCTIVE SCIENCES, Vol: 18, Pages: 296A-297A, ISSN: 1933-7191
Lei K, Sooranna SR, Bennett PR, et al., 2011, Glucocorticoid Receptor Is a Key Player That Mediates Progesterone Action in Human Myometrium, REPRODUCTIVE SCIENCES, Vol: 18, Pages: 157A-158A, ISSN: 1933-7191
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- Citations: 1
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
Lei K, Chen L, Sooranna SR, et al., 2011, Mechanical Stretch and Progesterone Action in Human Myometrium, REPRODUCTIVE SCIENCES, Vol: 18, Pages: 297A-297A, ISSN: 1933-7191
Hua R, Viney J, Sooranna SR, et al., 2011, Upregulation of Biologically Active Chemokines by Cytokines and Mechanical Stretch Via MAPK and NFκB Pathways in Human Myometrium, REPRODUCTIVE SCIENCES, Vol: 18, Pages: 313A-313A, 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.
Cryar B, Sooranna SR, Bennett PR, et al., 2010, The Small GTPase p21Ras Is Required for Stretch Induced Up-Regulation of COX-2 and IL-8 Via the MAPK Pathway in Uterine Smooth Muscle Cells, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 254A-255A, ISSN: 1933-7191
Chen L, Lei K, Sooranna SR, et al., 2010, The Effect of cAMP on PRE Promoter Activity in Presence or Absence of Progesterone, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 278A-278A, ISSN: 1933-7191
Lei K, Chen L, Sooranna SR, et al., 2010, The Effect of Pro-Inflammatory Transcription Factors on Progesterone Receptor B Transactivation in Human Myometrium, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 281A-282A, ISSN: 1933-7191
Lei K, Sooranna SR, Bennett PR, et al., 2010, The Effect of Cytokines and Prostaglandins on Nuclear Receptor CoRegulators in Human Myometrium, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 285A-285A, ISSN: 1933-7191
Terzidou V, Sooranna SR, Johnson M, et al., 2010, A Role for the SUMO Pathway in Human Labour., Pages: 71A-71A, ISSN: 1933-7191
Chen L, Sooranna SR, Bennett PR, et al., 2010, The Effect cAMP and Its Effectors on COX-2 Expression in Human Myomerium, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 278A-279A, ISSN: 1933-7191
Hua R, Sooranna SR, Bennett PR, et al., 2010, Changes in Chemokine and Chemokine Receptor Expression Occur Prior to Labour, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 280A-280A, ISSN: 1933-7191
Hua R, Sooranna SR, Bennett PR, et al., 2010, Cytokines Increase Chemokine Expression in Myometrium, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 280A-281A, ISSN: 1933-7191
Lei K, Chen L, Sooranna SR, et al., 2010, The Role of Cyclin Dependent Kinase 2 in Stretch-Induced Progesterone Receptor B Activation in Human Myometrium, 57th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 281A-281A, ISSN: 1933-7191
Lee Y, Sooranna S, Terzidou V, et al., 2010, Identification of Progesterone Responsive Genes in Human Myometrium, Pages: 156A-156A, ISSN: 1933-7191
Sooranna SR, Khanjani S, Grisby PL, et al., 2009, ENA-78 (CXCL5) Is Increased in Human Myometrium at Parturition, 56th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 76A-76A, ISSN: 1933-7191
Khanjani S, Sooranna SR, Melchionda M, et al., 2009, Myocytes as Immune Cells: NF-kappa B Regulates a Group of Immune/Inflammatory Genes, Pages: 117A-117A, ISSN: 1933-7191
Sooranna SR, Khajani S, Nelson SM, et al., 2009, The Effect of Stretch on Chemokine Expression in Human Uterine Myocytes, 56th Annual Meeting of the Society-for-Gynecologic-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 121A-121A, ISSN: 1933-7191
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