S.K. Munro

Publications (7)7.55 Total impact

• Article: Histone deacetylase inhibition by trichostatin A mitigates LPS induced TNFα and IL-10 production in human placental explants.

  S K Munro, M D Mitchell, A P Ponnampalam
  [show abstract] [hide abstract]
  ABSTRACT: INTRODUCTION: Cytokine expression by the placenta is known to change across pregnancy, and is altered in a number of pathologies; however the precise mechanisms of cytokine regulation in gestational tissues are not well understood. It has been previously reported that cytokine protein production in gestational tissues is regulated in a tissue-specific manner and appears to be epigenetically regulated. METHODS: In this study we investigated changes in cytokine mRNA expression and protein production by term placental explants maintained at 8% O2 in the presence or absence of lipopolysaccharide (LPS) (5 μg/mL) and the histone deacetylase inhibitor trichostatin A (TSA) (300 nM). RESULTS: As expected, exposure to LPS stimulated gene expression and protein production of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, as well as the anti-inflammatory cytokine IL-10. While TSA alone had little effect, TSA co-treatment mitigated the effects of LPS on TNFα and IL-10 protein production with an accompanying reduction in TNFα mRNA transcript levels detected. However, TSA had no significant effect on LPS induced IL-1β, IL-1ra, IL-6 or IL-8 mRNA expression or protein production. DISCUSSION: The data from this study show that TSA selectively mitigates the stimulatory effect of LPS on TNFα mRNA expression, TNFα protein production and IL-10 protein production. As there is no compensatory effect on IL-1β, IL-1ra, IL-6, or IL-8 mRNA expression or protein production, this results in a dysregulation of the cytokine balance. CONCLUSIONS: Insights into HDAC regulation of cytokine expression may provide novel therapeutic strategies for conditions associated with dysregulation of the cytokine network, such as preeclampsia and infection mediated preterm labor.
  Placenta 04/2013; · 3.69 Impact Factor
• Article: Epigenetic regulation of endometrium during the menstrual cycle.

  S K Munro, C M Farquhar, M D Mitchell, A P Ponnampalam
  [show abstract] [hide abstract]
  ABSTRACT: The endometrium undergoes morphological and functional changes during the menstrual cycle which are essential for uterine receptivity. These changes are driven by estrogen and progesterone and involve the fine control of many different genes-several of which have been identified as being epigenetically regulated. Epigenetic modification may therefore influence the functional changes in the endometrium required for successful implantation. There is, however, only limited information on epigenetic regulation in endometrium. We review the potential role of epigenetic regulation of key processes during the menstrual cycle and present our own findings following a preliminary study into global acetylation levels in the human endometrium. A changing epigenetic state is associated with the differentiation of stem cells into different lineages and thus may be involved in endometrial regeneration. Histone acetylation is implicated in the vascular endothelial growth factor pathway during angiogenesis, and studies using histone deacetylase inhibitors suggest an involvement in endometrial proliferation and differentiation. The processes of decidualization and implantation are also associated with epigenetic change and epigenetic modulators show variable expression across the menstrual cycle. Our own studies found that endometrial global histone acetylation, as determined by western blotting, changed throughout the menstrual cycle and correlated well with expected transcription activity during the different phases. This suggests that epigenetics may be involved in the regulation of endometrial gene expression during the menstrual cycle and that abnormal epigenetic modifications may therefore be associated with implantation failure and early pregnancy loss as well as with other endometrial pathologies.
  Molecular Human Reproduction 02/2010; 16(5):297-310. · 3.85 Impact Factor
• Article: Histone acetylation changes in the human endometrium during the menstrual cycle

  S.K. Munro, M D Mitchell, C.M. Farquhar, A.P. Ponnampalam
• Article: Epigenetic changes in human endometrium vary with stage of the menstrual cycle

  S.K. Munro, Z.L. Vincent, C.M. Farquhar, M D Mitchell, A.P. Ponnampalam
• Article: Epigenetic regulation of the inflammatory response in placenta

  M D Mitchell, D. DeSilva, S.K. Munro, A.P. Ponnampalam
• Article: Dynamic changes in the expressions of DNA methyltransferases (DNMTs) in placenta associated with labour in women

  Z.L. Vincent, S.K. Munro, A.P. Ponnampalam, M D Mitchell
• Article: Cytokine regulation during the formation of the fetal-maternal interface: Focus on cell-cell adhesion and remodelling of the extra-cellular matrix

  M. McEwan, R.J. Lins, S.K. Munro, Z.L. Vincent, A.P. Ponnampalam, M D Mitchell
  [show abstract] [hide abstract]
  ABSTRACT: The establishment of human pregnancy requires the orchestration of substantial cell differentiation and tissue remodelling processes in the context of a complex dialogue between the receptive endometrium and the implanting blastocyst, and is therefore dependent upon a complex sequence of signalling events. Cytokines play an important role in each step of implantation, modulating expression of adhesion molecules on both the fetal and maternal surfaces, regulating expression of the proteases that remodel the extra-cellular matrix, and promoting invasion and differentiation of trophoblasts. Here we review the role of cytokines in regulating the establishment of the fetal-maternal interface, with a particular focus on regulation of the functional expression of CAMs, the ECM and of the proteinases that modulate their function. © 2009 Elsevier Ltd. All rights reserved.