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Placenta. 2013 Jul;34(7):567-73. doi: 10.1016/j.placenta.2013.04.004. Epub 2013 Apr 25.

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

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1
The Liggins Institute, The University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.

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.

PMID:
23623485
DOI:
10.1016/j.placenta.2013.04.004
[Indexed for MEDLINE]
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